旋毛虫不同发育时期基因重组蛋白的免疫原性分析及保护性研究
|
摘要
旋毛虫病是一种重要的食源性人兽共患病，可以感染人和100多种哺乳动物，当人类生食或半生食含有感染期幼虫的肉类（如猪肉、马肉等）时，可感染旋毛虫病。在某些国家，由于饮食和烹饪习惯的改变，旋毛虫病被视为一种新兴的或重新出现的疾病，世界不同地区定期有人类感染旋毛虫病疫情的报道。鉴于旋毛虫病对动物饲养和食品安全具有较大的影响，研制可用于人类和家畜的抗旋毛虫感染疫苗将为该病的预防和控制提供一个有价值的工具。
在动物模型中已有基于旋毛虫虫体粗提物、ES产物、减毒沙门氏菌或重组蛋白疫苗的报道。在过去的十年中，已经研究了几种旋毛虫分泌的或与建立寄生/感染有关的蛋白作为重组疫苗的成分，在抗旋毛虫感染方面产生了部分保护作用。然而，由于在宿主中寄生虫抗原在发育期间的变异及多种分子参与寄生过程的建立，单独使用一种蛋白很难产生有效的免疫保护效力，因此，多种抗原联合疫苗可能产生有效的保护。
抵抗病原微生物侵袭最常用的方法是利用其天然抗原或重组蛋白抗原对宿主进行免疫，从而达到对宿主的保护。本实验室已利用感染旋毛虫26天猪血清分别从旋毛虫肠道感染性肌幼虫（inML）、3日龄成虫（Ad3）和新生幼虫（NBL）期cDNA文库中成功筛选得到旋毛虫肠道感染性肌幼虫期半胱氨酸蛋白酶抑制剂类似物基因（Ts-clp）、旋毛虫成虫期丝氨酸蛋白酶基因（Ts-Adsp）和旋毛虫新生幼虫期丝氨酸蛋白酶基因（Ts-NBLsp）；利用感染旋毛虫60天猪血清从旋毛虫肌幼虫（ML）期cDNA文库中筛选获得旋毛虫肌幼虫期丝氨酸蛋白酶抑制剂基因（Ts-serpin）。本研究选用来自旋毛虫不同发育时期cDNA文库中的4种高丰度基因，利用实验室已经成功构建的以pET-28a为载体的4种基因重组表达菌，对其反应原性和免疫原性进行分析，以期研制出高效安全的旋毛虫重组蛋白联合疫苗。
首先，诱导表达4种重组蛋白并利用亲和层析技术进行纯化，经鉴定纯化条带单一且与预期大小相符，利用旋毛虫感染猪、鼠血清对重组蛋白进行鉴定，结果显示，4种重组蛋白均可与旋毛虫感染猪、鼠血清反应，说明旋毛虫不同发育时期基因重组蛋白具有较强的反应原性，可与自然感染和人工感染的旋毛虫抗血清反应。纯化后的4种重组蛋白分别免疫小鼠，制备多克隆抗体，将4种多克隆抗体与旋毛虫ES产物、虫体粗提物抗原反应，结果显示，4种多克隆抗体均可识别天然Ts-clp、Ts-Adsp、Ts-NBLsp和Ts-serpin蛋白。因此，4种重组蛋白均为高反应原性抗原，并且其抗血清可与天然抗原产生免疫反应，对于旋毛虫病的诊断及疫苗的研制具有一定价值。
其次，利用免疫荧光技术分析4种抗原基因的表达特性，结果显示，重组蛋白抗血清在旋毛虫成虫、新生幼虫、肌幼虫虫体表面均有表达，表明4种蛋白参与宿主-寄生虫相互作用，可作为抗旋毛虫疫苗的良好候选抗原。将4种高反应原性抗原与弗氏佐剂乳化后分别免疫小鼠，并于三免后经口感染旋毛虫肌幼虫，鉴定重组抗原的免疫原性及保护率，结果显示，与PBS对照组相比，rTs-clp、rTs-Adsp、rTs-NBLsp和rTs-serpin免疫组小鼠减虫率分别为：24.42%、41.31%、22.39%、30.5%。重组蛋白免疫小鼠均可诱导体液及细胞免疫应答，表现为特异性IgG抗体升高和混合型Th1/Th2反应，显示为Th1（IFN-γ、IL-2）和Th2（IL-4、IL-10、IL-13）型细胞因子升高，并以Th2型占优势。因此，旋毛虫不同发育时期基因重组蛋白具有较强的免疫原性并可诱导机体产生部分保护性免疫，可用作研制抗旋毛虫病有效疫苗的候选抗原。
最后，优化疫苗的免疫程序（以对旋毛虫肌幼虫产生最低保护作用的rTs-NBLsp为例），为重组蛋白联合疫苗的研制奠定基础。由于弗氏佐剂毒性较强，甚至不适合用作大规模动物实验，本研究对免疫佐剂进行优化，结果显示，铝佐剂可以诱导机体产生与弗氏佐剂相似的免疫反应且毒性较低，因此选用铝佐剂作为联合疫苗的免疫佐剂；使用三种不同抗原剂量（10、20和50μg）免疫小鼠，结果显示20μg重组蛋白免疫组可诱导与50μg免疫组相似的免疫反应，且不改变免疫反应的类型，因此选择20μg作为联合疫苗中每种重组蛋白的免疫剂量。根据上述的疫苗优化程序，将不同发育时期高免疫原性重组蛋白与铝佐剂乳化后联合免疫小鼠（免疫剂量为每种蛋白20μg），结果显示，重组蛋白联合疫苗可诱导机体产生强烈的体液和细胞免疫反应，且每种抗原之间具有协同作用，均诱导机体产生对抗旋毛虫感染有利的免疫反应，使疫苗减虫率提高至70.9%，与单独免疫组相比减虫率大大提高。
综上所述，本研究表明多种重组蛋白联合免疫小鼠在预防旋毛虫病方面可以成为一种十分有前景的方法。本研究结果显示，抗旋毛虫感染有效的疫苗应该由多种寄生虫抗原组成，而且有效的蛋白成分可以在机体中发挥协同作用，诱导宿主产生强烈的保护性免疫反应。
Trichinellosis is an important foodborne zoonotic disease which infects humanand more than100mammals. Human infection occurs by eating raw or undercookedmeats containing infective larvae, such as pork and horsemeat. In some countries dueto changes in diet and cooking habits, trichinellosis is regarded as an emerging orre-emerging disease. It is regularly reported of human outbreaks in different parts ofthe world. Because trichinellosis has major impacts on animal husbandry and foodsafety, development of a vaccine defence against Trichinella spiralis (T. spiralis)larvae infection in domestic animals and humans would provide a valuable tool fordisease prevention and control.
T. spiralis crude antigen preparations, excretory-secretory (ES) products,attenuated Salmonella or recombinant proteins-based vaccines have been reported inanimal models. In the past decade, several proteins which are secreted by T. spiralis orrelated to establishing parasitism/infection have been studied as composition of therecombinant vaccine and induce partial protection against T. spiralis larvae infection.However, due to the parasite antigens changes during the development in the host andvariety of molecules are involved in establishment of parasitic process, it is difficult toinduce high levels of protection with a single antigen. Therefore, combination ofmultiple recombinant proteins may induce effective protection.
The most common method to elicit protection against pathogenic microorganismis native immunization with immunogenic native or recombinant proteins which areimportant for pathogenicity. Our laboratory had immunoscreened T. spiralis intestinalphase infective larvae (inML),3-day-old adults (Ad3) and newborn larvae (NBL)cDNA library with T. spiralis infected26days pig serum and cystatin-like protein of T.Spiralis inML stage (Ts-clp), serine protease gene of adult stage (Ts-Adsp) and serineprotease gene of NBL stage (Ts-NBLsp) were successfully screened; and musclelarvae (ML) cDNA library was screening with T. spiralis infected60days pig serum, a gene encoding serine protease inhibitor (Ts-serpin) was successfully screened. Thisresearch chooses four high-abundance genes from different cDNA libraries, and usesthe four recombinant proteins in expression vector pET-28a which have beenconstructed by our laboratory. Its reactogenicity and immunogenicity was analyzed inorder to develop a highly efficient and safe vaccine which combination of multiplerecombinant proteins.
First, the four recombinant proteins were induced, expressed and purified byaffinity chromatography. After identified with SDS-PAGE, purified recombinantproteins each appeared as a single band and the molecular mass was consistent withthe expected size. The reactogenicity of recombinant proteins was identified with pigsand mice sera infected with T. spiralis, the results showed that the purified fourrecombinant proteins were recognized by the sera from T. spiralis infected pig andmouse. It suggested that the recombinant proteins of T. spiralis at differentdevelopment stages had high reactogenicity and can recognize both naturally infectedand laboratory infected T. spiralis antiserum. Polyclonal antibodies were preparedfrom purified recombinant proteins immunized mice, which were added to ESproducts and crude extract antigen of T. spiralis. These results exhibited that therecombinant proteins antiserum could recognize natural Ts-clp, Ts-Adsp, Ts-NBLspand Ts-serpin protein. Therefore, the four recombinant proteins are high reactogenicityantigen and can induce immune response with natural antigens. It has a certain valuein diagnosis and vaccine development of trichinellosis.
Secondly, the antigen gene expression characteristics were analyzed byimmunofluorescence techniques, the results exhibited that the antisera of recombinantproteins were expressed on the surface of Ad, NBL and ML of T. spiralis. It suggeststhat these four proteins are involved in host-parasite interaction and are goodcandidates for the control of trichinellosis. We immunized Balb/c mice with the fourhigh reactogenicity antigens, respectively, in combination with Freund’s adjuvant andsubsequently challenged with T. spiralis larvae to determine the immunogenicity andprotection rate of recombinant antigens. The results exhibited that mice immunizedwith rTs-clp, rTs-Adsp, rTs-NBLsp or rTs-serpin exhibited an average reduction in themuscle larvae burden of24.42%,41.31%,22.39%and30.5%, respectively, relative to the control group. Immunization with the recombinant proteins induced both humoraland cellular immune responses, which manifested as elevated specific IgG antibodiesand a mixed Th1/Th2response, as determined by Th1(IFN-γ and IL-2) and Th2(IL-4,IL-10and IL-13) cytokine profiling, with the Th2predominant. Therefore, the fourrecombinant proteins of T. spiralis at different development stages have highimmunogenic and can induce partial protective immunity. They can be used aseffective vaccine candidates defence against trichinellosis.
Finally, the immunization scheme was optimized to develop a vaccine whichcombination of four recombinant proteins (with the minimum protection of T. spiralismuscle larvae of rTs-NBLsp as an example). Due to the highly toxic of Freund’sadjuvant and even unsuitable for animal experiments, the study was taken to optimizethe condition of immune adjuvants. The results suggest that alum adjuvant can inducesimilar immune response to Freund’s adjuvant, and it has less toxic, so we choosealum as multi-antigenic vaccine adjuvant. Three different antigen doses (10,20or50μg) were immunized mice, respectively. The results suggested that the20μgrecombinant protein-immunized group could induce a similar immune response to50μg recombinant protein-immunized group, and the type of immune response did notchange. So we chose the dose of20μg for each recombinant protein asmulti-antigenic vaccine immunization dose. According to the optimize schemes above,the high immunogenicity recombinant proteins of T. spiralis at different developmentstages were immunized mice by20μg each. The results showed that the vaccinewhich combination of four recombinant proteins can induce strong humoral andcellular immune responses, and each antigen had a synergistic effect, which inducedfavorable immune response against T. spiralis infection. The vaccine whichcombination of four recombinant proteins can induce a higher reduction in the musclelarvae burden to70.9%, which is greatly increased compared with the singleimmunzed group.
In conclusion, this study suggested that immunization with a mixture ofrecombinant antigens could be a very promising tool in immunoprophylaxis oftrichinellosis. Our results suggested that an effective vaccine defence againstTrichinella infection should be composed of a variety of parasite antigens and that the proper proteins could be equally effective, leading to strong protection againstparasite invasion.
在动物模型中已有基于旋毛虫虫体粗提物、ES产物、减毒沙门氏菌或重组蛋白疫苗的报道。在过去的十年中，已经研究了几种旋毛虫分泌的或与建立寄生/感染有关的蛋白作为重组疫苗的成分，在抗旋毛虫感染方面产生了部分保护作用。然而，由于在宿主中寄生虫抗原在发育期间的变异及多种分子参与寄生过程的建立，单独使用一种蛋白很难产生有效的免疫保护效力，因此，多种抗原联合疫苗可能产生有效的保护。
抵抗病原微生物侵袭最常用的方法是利用其天然抗原或重组蛋白抗原对宿主进行免疫，从而达到对宿主的保护。本实验室已利用感染旋毛虫26天猪血清分别从旋毛虫肠道感染性肌幼虫（inML）、3日龄成虫（Ad3）和新生幼虫（NBL）期cDNA文库中成功筛选得到旋毛虫肠道感染性肌幼虫期半胱氨酸蛋白酶抑制剂类似物基因（Ts-clp）、旋毛虫成虫期丝氨酸蛋白酶基因（Ts-Adsp）和旋毛虫新生幼虫期丝氨酸蛋白酶基因（Ts-NBLsp）；利用感染旋毛虫60天猪血清从旋毛虫肌幼虫（ML）期cDNA文库中筛选获得旋毛虫肌幼虫期丝氨酸蛋白酶抑制剂基因（Ts-serpin）。本研究选用来自旋毛虫不同发育时期cDNA文库中的4种高丰度基因，利用实验室已经成功构建的以pET-28a为载体的4种基因重组表达菌，对其反应原性和免疫原性进行分析，以期研制出高效安全的旋毛虫重组蛋白联合疫苗。
首先，诱导表达4种重组蛋白并利用亲和层析技术进行纯化，经鉴定纯化条带单一且与预期大小相符，利用旋毛虫感染猪、鼠血清对重组蛋白进行鉴定，结果显示，4种重组蛋白均可与旋毛虫感染猪、鼠血清反应，说明旋毛虫不同发育时期基因重组蛋白具有较强的反应原性，可与自然感染和人工感染的旋毛虫抗血清反应。纯化后的4种重组蛋白分别免疫小鼠，制备多克隆抗体，将4种多克隆抗体与旋毛虫ES产物、虫体粗提物抗原反应，结果显示，4种多克隆抗体均可识别天然Ts-clp、Ts-Adsp、Ts-NBLsp和Ts-serpin蛋白。因此，4种重组蛋白均为高反应原性抗原，并且其抗血清可与天然抗原产生免疫反应，对于旋毛虫病的诊断及疫苗的研制具有一定价值。
其次，利用免疫荧光技术分析4种抗原基因的表达特性，结果显示，重组蛋白抗血清在旋毛虫成虫、新生幼虫、肌幼虫虫体表面均有表达，表明4种蛋白参与宿主-寄生虫相互作用，可作为抗旋毛虫疫苗的良好候选抗原。将4种高反应原性抗原与弗氏佐剂乳化后分别免疫小鼠，并于三免后经口感染旋毛虫肌幼虫，鉴定重组抗原的免疫原性及保护率，结果显示，与PBS对照组相比，rTs-clp、rTs-Adsp、rTs-NBLsp和rTs-serpin免疫组小鼠减虫率分别为：24.42%、41.31%、22.39%、30.5%。重组蛋白免疫小鼠均可诱导体液及细胞免疫应答，表现为特异性IgG抗体升高和混合型Th1/Th2反应，显示为Th1（IFN-γ、IL-2）和Th2（IL-4、IL-10、IL-13）型细胞因子升高，并以Th2型占优势。因此，旋毛虫不同发育时期基因重组蛋白具有较强的免疫原性并可诱导机体产生部分保护性免疫，可用作研制抗旋毛虫病有效疫苗的候选抗原。
最后，优化疫苗的免疫程序（以对旋毛虫肌幼虫产生最低保护作用的rTs-NBLsp为例），为重组蛋白联合疫苗的研制奠定基础。由于弗氏佐剂毒性较强，甚至不适合用作大规模动物实验，本研究对免疫佐剂进行优化，结果显示，铝佐剂可以诱导机体产生与弗氏佐剂相似的免疫反应且毒性较低，因此选用铝佐剂作为联合疫苗的免疫佐剂；使用三种不同抗原剂量（10、20和50μg）免疫小鼠，结果显示20μg重组蛋白免疫组可诱导与50μg免疫组相似的免疫反应，且不改变免疫反应的类型，因此选择20μg作为联合疫苗中每种重组蛋白的免疫剂量。根据上述的疫苗优化程序，将不同发育时期高免疫原性重组蛋白与铝佐剂乳化后联合免疫小鼠（免疫剂量为每种蛋白20μg），结果显示，重组蛋白联合疫苗可诱导机体产生强烈的体液和细胞免疫反应，且每种抗原之间具有协同作用，均诱导机体产生对抗旋毛虫感染有利的免疫反应，使疫苗减虫率提高至70.9%，与单独免疫组相比减虫率大大提高。
综上所述，本研究表明多种重组蛋白联合免疫小鼠在预防旋毛虫病方面可以成为一种十分有前景的方法。本研究结果显示，抗旋毛虫感染有效的疫苗应该由多种寄生虫抗原组成，而且有效的蛋白成分可以在机体中发挥协同作用，诱导宿主产生强烈的保护性免疫反应。
Trichinellosis is an important foodborne zoonotic disease which infects humanand more than100mammals. Human infection occurs by eating raw or undercookedmeats containing infective larvae, such as pork and horsemeat. In some countries dueto changes in diet and cooking habits, trichinellosis is regarded as an emerging orre-emerging disease. It is regularly reported of human outbreaks in different parts ofthe world. Because trichinellosis has major impacts on animal husbandry and foodsafety, development of a vaccine defence against Trichinella spiralis (T. spiralis)larvae infection in domestic animals and humans would provide a valuable tool fordisease prevention and control.
T. spiralis crude antigen preparations, excretory-secretory (ES) products,attenuated Salmonella or recombinant proteins-based vaccines have been reported inanimal models. In the past decade, several proteins which are secreted by T. spiralis orrelated to establishing parasitism/infection have been studied as composition of therecombinant vaccine and induce partial protection against T. spiralis larvae infection.However, due to the parasite antigens changes during the development in the host andvariety of molecules are involved in establishment of parasitic process, it is difficult toinduce high levels of protection with a single antigen. Therefore, combination ofmultiple recombinant proteins may induce effective protection.
The most common method to elicit protection against pathogenic microorganismis native immunization with immunogenic native or recombinant proteins which areimportant for pathogenicity. Our laboratory had immunoscreened T. spiralis intestinalphase infective larvae (inML),3-day-old adults (Ad3) and newborn larvae (NBL)cDNA library with T. spiralis infected26days pig serum and cystatin-like protein of T.Spiralis inML stage (Ts-clp), serine protease gene of adult stage (Ts-Adsp) and serineprotease gene of NBL stage (Ts-NBLsp) were successfully screened; and musclelarvae (ML) cDNA library was screening with T. spiralis infected60days pig serum, a gene encoding serine protease inhibitor (Ts-serpin) was successfully screened. Thisresearch chooses four high-abundance genes from different cDNA libraries, and usesthe four recombinant proteins in expression vector pET-28a which have beenconstructed by our laboratory. Its reactogenicity and immunogenicity was analyzed inorder to develop a highly efficient and safe vaccine which combination of multiplerecombinant proteins.
First, the four recombinant proteins were induced, expressed and purified byaffinity chromatography. After identified with SDS-PAGE, purified recombinantproteins each appeared as a single band and the molecular mass was consistent withthe expected size. The reactogenicity of recombinant proteins was identified with pigsand mice sera infected with T. spiralis, the results showed that the purified fourrecombinant proteins were recognized by the sera from T. spiralis infected pig andmouse. It suggested that the recombinant proteins of T. spiralis at differentdevelopment stages had high reactogenicity and can recognize both naturally infectedand laboratory infected T. spiralis antiserum. Polyclonal antibodies were preparedfrom purified recombinant proteins immunized mice, which were added to ESproducts and crude extract antigen of T. spiralis. These results exhibited that therecombinant proteins antiserum could recognize natural Ts-clp, Ts-Adsp, Ts-NBLspand Ts-serpin protein. Therefore, the four recombinant proteins are high reactogenicityantigen and can induce immune response with natural antigens. It has a certain valuein diagnosis and vaccine development of trichinellosis.
Secondly, the antigen gene expression characteristics were analyzed byimmunofluorescence techniques, the results exhibited that the antisera of recombinantproteins were expressed on the surface of Ad, NBL and ML of T. spiralis. It suggeststhat these four proteins are involved in host-parasite interaction and are goodcandidates for the control of trichinellosis. We immunized Balb/c mice with the fourhigh reactogenicity antigens, respectively, in combination with Freund’s adjuvant andsubsequently challenged with T. spiralis larvae to determine the immunogenicity andprotection rate of recombinant antigens. The results exhibited that mice immunizedwith rTs-clp, rTs-Adsp, rTs-NBLsp or rTs-serpin exhibited an average reduction in themuscle larvae burden of24.42%,41.31%,22.39%and30.5%, respectively, relative to the control group. Immunization with the recombinant proteins induced both humoraland cellular immune responses, which manifested as elevated specific IgG antibodiesand a mixed Th1/Th2response, as determined by Th1(IFN-γ and IL-2) and Th2(IL-4,IL-10and IL-13) cytokine profiling, with the Th2predominant. Therefore, the fourrecombinant proteins of T. spiralis at different development stages have highimmunogenic and can induce partial protective immunity. They can be used aseffective vaccine candidates defence against trichinellosis.
Finally, the immunization scheme was optimized to develop a vaccine whichcombination of four recombinant proteins (with the minimum protection of T. spiralismuscle larvae of rTs-NBLsp as an example). Due to the highly toxic of Freund’sadjuvant and even unsuitable for animal experiments, the study was taken to optimizethe condition of immune adjuvants. The results suggest that alum adjuvant can inducesimilar immune response to Freund’s adjuvant, and it has less toxic, so we choosealum as multi-antigenic vaccine adjuvant. Three different antigen doses (10,20or50μg) were immunized mice, respectively. The results suggested that the20μgrecombinant protein-immunized group could induce a similar immune response to50μg recombinant protein-immunized group, and the type of immune response did notchange. So we chose the dose of20μg for each recombinant protein asmulti-antigenic vaccine immunization dose. According to the optimize schemes above,the high immunogenicity recombinant proteins of T. spiralis at different developmentstages were immunized mice by20μg each. The results showed that the vaccinewhich combination of four recombinant proteins can induce strong humoral andcellular immune responses, and each antigen had a synergistic effect, which inducedfavorable immune response against T. spiralis infection. The vaccine whichcombination of four recombinant proteins can induce a higher reduction in the musclelarvae burden to70.9%, which is greatly increased compared with the singleimmunzed group.
In conclusion, this study suggested that immunization with a mixture ofrecombinant antigens could be a very promising tool in immunoprophylaxis oftrichinellosis. Our results suggested that an effective vaccine defence againstTrichinella infection should be composed of a variety of parasite antigens and that the proper proteins could be equally effective, leading to strong protection againstparasite invasion.
引文
[1] FU B Q, LIU M Y, KAPEL C M, et al. Molecular cloning of a cDNA encoding aputative cuticle collagen of Trichinella spiralis [J]. Vet Parasitol,2005,132(1-2):31-35.
[2] BIOREAU P, VAYSSIER M, FABIEN J F, et al. Characterization of elevenantigenic groups in Trichinella genus and identification of stage and speciesmarkers [J]. Parasitology,1997,115(Pt6):641-651.
[3] DEVILLE S, POOTER A, AUCOUTURIER J, et al. Influence of adjuvantformulation on the induced protection of mice immunized with total solubleantigen of Trichinella spiralis [J]. Vet Parasitol,2005,132(1-2):75-80.
[4] LIGHTOWLERS M W. Cestode vaccines: origins, current status and futureprospects [J]. Parasitology,2006,133Suppl: S27-42.
[5] LUSTIGMAN S, JAMES E R, TAWE W, et al. Towards a recombinant antigenvaccine against Onchocerca volvulus [J]. Trends Parasitol,2002,18(3):135-141.
[6] TRAP C, FU B, LE GUERHIER F, et al. Cloning and analysis of a cDNAencoding a putative serine protease comprising two trypsin-like domains ofTrichinella spiralis [J]. Parasitol Res,2006,98(4):288-294.
[7] ALLEN J E, MAIZELS R M. Diversity and dialogue in immunity to helminths[J]. Nat Rev Immunol,2011,11(6):375-388.
[8] MATISZ C E, MCDOUGALL J J, SHARKEY K A, et al. Helminth parasitesand the modulation of joint inflammation [J]. J Parasitol Res,2011,2011(942616).
[9] FLEMING J O. Helminths and multiple sclerosis: will old friends give us newtreatments for MS?[J]. J Neuroimmunol,2011,233(1-2):3-5.
[10] FLEMING J O, ISAAK A, LEE J E, et al. Probiotic helminth administration inrelapsing-remitting multiple sclerosis: a phase1study [J]. Mult Scler,2011,17(6):743-754.
[11] HE Y, LI J, ZHUANG W, et al. The inhibitory effect against collagen-inducedarthritis by Schistosoma japonicum infection is infection stage-dependent [J].BMC Immunol,2010,11(28).
[12] MCKAY D M. The therapeutic helminth?[J]. Trends Parasitol,2009,25(3):109-114.
[13] REIS E SOUSA C, HIENY S, SCHARTON-KERSTEN T, et al. In vivomicrobial stimulation induces rapid CD40ligand-independent production ofinterleukin12by dendritic cells and their redistribution to T cell areas [J]. J ExpMed,1997,186(11):1819-1829.
[14] MAIZELS R M, BALIC A, GOMEZ-ESCOBAR N, et al. Helminthparasites--masters of regulation [J]. Immunol Rev,2004,201:89-116.
[15] VAN RIET E, EVERTS B, RETRA K, et al. Combined TLR2and TLR4ligationin the context of bacterial or helminth extracts in human monocyte deriveddendritic cells: molecular correlates for Th1/Th2polarization [J]. BMC Immunol,2009,10(9).
[16] CERVI L, MACDONALD A S, KANE C, et al. Cutting edge: dendritic cellscopulsed with microbial and helminth antigens undergo modified maturation,segregate the antigens to distinct intracellular compartments, and concurrentlyinduce microbe-specific Th1and helminth-specific Th2responses [J]. J Immunol,2004,172(4):2016-2020.
[17] WHELAN M, HARNETT M M, HOUSTON K M, et al. A filarialnematode-secreted product signals dendritic cells to acquire a phenotype thatdrives development of Th2cells [J]. J Immunol,2000,164(12):6453-6460.
[18] BALIC A, HARCUS Y, HOLLAND M J, et al. Selective maturation of dendriticcells by Nippostrongylus brasiliensis-secreted proteins drives Th2immuneresponses [J]. Eur J Immunol,2004,34(11):3047-3059.
[19] GRAINGER J R, SMITH K A, HEWITSON J P, et al. Helminth secretionsinduce de novo T cell Foxp3expression and regulatory function through theTGF-beta pathway [J]. J Exp Med,2010,207(11):2331-2341.
[20] BEITING D P, GAGLIARDO L F, HESSE M, et al. Coordinated control ofimmunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, andTGF-beta [J]. J Immunol,2007,178(2):1039-1047.
[21] WU Z, SOFRONIC-MILOSAVLJEVIC L, NAGANO I, et al. Trichinellaspiralis: nurse cell formation with emphasis on analogy to muscle cell repair [J].Parasit Vectors,2008,1(1):27.
[22] NAGANO I, WU Z, TAKAHASHI Y. Functional genes and proteins ofTrichinella spp [J]. Parasitol Res,2009,104(2):197-207.
[23] ELSE K J. Have gastrointestinal nematodes outwitted the immune system?[J].Parasite Immunol,2005,27(10-11):407-415.
[24] MOSMANN T R. Cytokine secretion patterns and cross-regulation of T cellsubsets [J]. Immunol Res,1991,10(3-4):183-188.
[25] ISHIKAWA N, GOYAL P K, MAHIDA Y R, et al. Early cytokine responsesduring intestinal parasitic infections [J]. Immunology,1998,93(2):257-263.
[26] FINNEY C A, TAYLOR M D, WILSON M S, et al. Expansion and activation ofCD4+CD25+regulatory T cells in Heligmosomoides polygyrus infection [J]. EurJ Immunol,2007,37(7):1874-1886.
[27] TAYLOR J J, MOHRS M, PEARCE E J. Regulatory T cell responses develop inparallel to Th responses and control the magnitude and phenotype of the Theffector population [J]. J Immunol,2006,176(10):5839-5847.
[28] SHER A, PEARCE E, KAYE P. Shaping the immune response to parasites: roleof dendritic cells [J]. Curr Opin Immunol,2003,15(4):421-429.
[29] KANE C M, CERVI L, SUN J, et al. Helminth antigens modulate TLR-initiateddendritic cell activation [J]. J Immunol,2004,173(12):7454-7461.
[30] SEGURA M, SU Z, PICCIRILLO C, et al. Impairment of dendritic cell functionby excretory-secretory products: a potential mechanism for nematode-inducedimmunosuppression [J]. Eur J Immunol,2007,37(7):1887-1904.
[31] VAN RIET E, HARTGERS F C, YAZDANBAKHSH M. Chronic helminthinfections induce immunomodulation: consequences and mechanisms [J].Immunobiology,2007,212(6):475-490.
[32] MACDONALD A S, MAIZELS R M. Alarming dendritic cells for Th2induction [J]. J Exp Med,2008,205(1):13-17.
[33] ILIC N, GRUDEN-MOVSESIJAN A, SOFRONIC-MILOSAVLJEVIC L.Trichinella spiralis: shaping the immune response [J]. Immunol Res,2012,52(1-2):111-119.
[34] ILIC N, WORTHINGTON J J, GRUDEN-MOVSESIJAN A, et al. Trichinellaspiralis antigens prime mixed Th1/Th2response but do not induce de novogeneration of Foxp3+T cells in vitro [J]. Parasite Immunol,2011,33(10):572-582.
[35] ILIC N, COLIC M, GRUDEN-MOVSESIJAN A, et al. Characterization of ratbone marrow dendritic cells initially primed by Trichinella spiralis antigens [J].Parasite Immunol,2008,30(9):491-495.
[36] LEECH M D, GRENCIS R K. Induction of enhanced immunity to intestinalnematodes using IL-9-producing dendritic cells [J]. J Immunol,2006,176(4):2505-2511.
[37] LANGELAAR M, ARANZAMENDI C, FRANSSEN F, et al. Suppression ofdendritic cell maturation by Trichinella spiralis excretory/secretory products [J].Parasite Immunol,2009,31(10):641-645.
[38] THOMAS P G, CARTER M R, ATOCHINA O, et al. Maturation of dendriticcell2phenotype by a helminth glycan uses a Toll-like receptor4-dependentmechanism [J]. J Immunol,2003,171(11):5837-5841.
[39] JENKINS S J, MOUNTFORD A P. Dendritic cells activated with productsreleased by schistosome larvae drive Th2-type immune responses, which can beinhibited by manipulation of CD40costimulation [J]. Infect Immun,2005,73(1):395-402.
[40] MARSHALL F A, PEARCE E J. Uncoupling of induced protein processingfrom maturation in dendritic cells exposed to a highly antigenic preparation froma helminth parasite [J]. J Immunol,2008,181(11):7562-7570.
[41] PONCINI C V, ALBA SOTO C D, BATALLA E, et al. Trypanosoma cruziinduces regulatory dendritic cells in vitro [J]. Infect Immun,2008,76(6):2633-2641.
[42] BOUSHERI S, CAO H. New insight into the role of dendritic cells in malariaimmune pathogenesis [J]. Trends Parasitol,2008,24(5):199-200.
[43] REVEST M, DONAGHY L, CABILLIC F, et al. Comparison of theimmunomodulatory effects of L. donovani and L. major excreted-secretedantigens, particulate and soluble extracts and viable parasites on human dendriticcells [J]. Vaccine,2008,26(48):6119-6123.
[44] WIETHE C, DEBUS A, MOHRS M, et al. Dendritic cell differentiation state andtheir interaction with NKT cells determine Th1/Th2differentiation in the murinemodel of Leishmania major infection [J]. J Immunol,2008,180(7):4371-4381.
[45] MANICKASINGHAM S P, EDWARDS A D, SCHULZ O, et al. The ability ofmurine dendritic cell subsets to direct T helper cell differentiation is dependenton microbial signals [J]. Eur J Immunol,2003,33(1):101-107.
[46] CHANG J, KUNKEL S L, CHANG C H. Negative regulation ofMyD88-dependent signaling by IL-10in dendritic cells [J]. Proc Natl Acad Sci US A,2009,106(43):18327-18332.
[47] XIA C Q, KAO K J. Suppression of interleukin-12production throughendogenously secreted interleukin-10in activated dendritic cells: involvement ofactivation of extracellular signal-regulated protein kinase [J]. Scand J Immunol,2003,58(1):23-32.
[48] MUTHANA M, FAIRBURN B, MIRZA S, et al. Identification of a rat bonemarrow-derived dendritic cell population which secretes both IL-10and IL-12:evidence against a reciprocal relationship between IL-10and IL-12secretion [J].Immunobiology,2006,211(5):391-402.
[49] SALLUSTO F, LANZAVECCHIA A. The instructive role of dendritic cells onT-cell responses [J]. Arthritis Res,2002,4Suppl3: S127-132.
[50] CARVALHO L P, PEARCE E J, SCOTT P. Functional dichotomy of dendriticcells following interaction with Leishmania braziliensis: infected cells producehigh levels of TNF-alpha, whereas bystander dendritic cells are activated topromote T cell responses [J]. J Immunol,2008,181(9):6473-6480.
[51] VASQUEZ R E, XIN L, SOONG L. Effects of CXCL10on dendritic cell andCD4+T-cell functions during Leishmania amazonensis infection [J]. InfectImmun,2008,76(1):161-169.
[52] SHAW J, GRUND V, DURLING L, et al. Dendritic cells pulsed with arecombinant chlamydial major outer membrane protein antigen elicit a CD4+type2rather than type1immune response that is not protective [J]. InfectImmun,2002,70(3):1097-1105.
[53] KOYASU S, MORO K, TANABE M, et al. Natural helper cells: a new player inthe innate immune response against helminth infection [J]. Adv Immunol,2010,108:21-44.
[54] SAENZ S A, NOTI M, ARTIS D. Innate immune cell populations function asinitiators and effectors in Th2cytokine responses [J]. Trends Immunol,2010,31(11):407-413.
[55] MACDONALD A S, ARAUJO M I, PEARCE E J. Immunology of parasitichelminth infections [J]. Infect Immun,2002,70(2):427-433.
[56] GRUDEN-MOVSESIJAN A, ILIC N, COLIC M, et al. The impact ofTrichinella spiralis excretory-secretory products on dendritic cells [J]. CompImmunol Microbiol Infect Dis,2011,34(5):429-439.
[57] GRUDEN-MOVSESIJAN A, ILIC N, MOSTARICA-STOJKOVIC M, et al.Mechanisms of modulation of experimental autoimmune encephalomyelitis bychronic Trichinella spiralis infection in Dark Agouti rats [J]. Parasite Immunol,2010,32(6):450-459.
[58] MALDONADO R A, VON ANDRIAN U H. How tolerogenic dendritic cellsinduce regulatory T cells [J]. Adv Immunol,2010,108:111-165.
[59] BABU S, BLAUVELT C P, KUMARASWAMI V, et al. Regulatory networksinduced by live parasites impair both Th1and Th2pathways in patent lymphaticfilariasis: implications for parasite persistence [J]. J Immunol,2006,176(5):3248-3256.
[60] SAKAGUCHI S, ONO M, SETOGUCHI R, et al. Foxp3+CD25+CD4+naturalregulatory T cells in dominant self-tolerance and autoimmune disease [J].Immunol Rev,2006,212:8-27.
[61] SUTHERLAND I A, LEATHWICK D M. Anthelmintic resistance in nematodeparasites of cattle: a global issue?[J]. Trends Parasitol,2011,27(4):176-181.
[62] HOSTE H, TORRES-ACOSTA J F. Non chemical control of helminths inruminants: adapting solutions for changing worms in a changing world [J]. VetParasitol,2011,180(1-2):144-154.
[63] CLAEREBOUT E, KNOX D P, VERCRUYSSE J. Current research and futureprospects in the development of vaccines against gastrointestinal nematodes incattle [J]. Expert Rev Vaccines,2003,2(1):147-157.
[64] MEEUSEN E N, PIEDRAFITA D. Exploiting natural immunity to helminthparasites for the development of veterinary vaccines [J]. Int J Parasitol,2003,33(11):1285-1290.
[65] VERCRUYSSE J, KNOX D P, SCHETTERS T P, et al. Veterinary parasiticvaccines: pitfalls and future directions [J]. Trends Parasitol,2004,20(10):488-492.
[66] SMITH W D, ZARLENGA D S. Developments and hurdles in generatingvaccines for controlling helminth parasites of grazing ruminants [J]. Vet Parasitol,2006,139(4):347-359.
[67] BISSET S A, MORRIS C A, MCEWAN J C, et al. Breeding sheep in NewZealand that are less reliant on anthelmintics to maintain health and productivity[J]. N Z Vet J,2001,49(6):236-246.
[68] URBAN J F, JR., KATONA I M, PAUL W E, et al. Interleukin4is important inprotective immunity to a gastrointestinal nematode infection in mice [J]. ProcNatl Acad Sci U S A,1991,88(13):5513-5517.
[69] FINKELMAN F D, MADDEN K B, CHEEVER A W, et al. Effects ofinterleukin12on immune responses and host protection in mice infected withintestinal nematode parasites [J]. J Exp Med,1994,179(5):1563-1572.
[70] SHAKYA K P, MILLER J E, HOROHOV D W. A Th2type of immuneresponse is associated with increased resistance to Haemonchus contortus innaturally infected Gulf Coast Native lambs [J]. Vet Parasitol,2009,163(1-2):57-66.
[71] RAINBIRD M A, MACMILLAN D, MEEUSEN E N. Eosinophil-mediatedkilling of Haemonchus contortus larvae: effect of eosinophil activation and roleof antibody, complement and interleukin-5[J]. Parasite Immunol,1998,20(2):93-103.
[72] BALIC A, BOWLES V M, MEEUSEN E N. Mechanisms of immunity toHaemonchus contortus infection in sheep [J]. Parasite Immunol,2002,24(1):39-46.
[73] BALIC A, CUNNINGHAM C P, MEEUSEN E N. Eosinophil interactions withHaemonchus contortus larvae in the ovine gastrointestinal tract [J]. ParasiteImmunol,2006,28(3):107-115.
[74] SHAW R, PFEFFER A, BISCHOF R. Ovine IgE and its role in immunologicalprotection and disease [J]. Vet Immunol Immunopathol,2009,132(1):31-40.
[75] KATARIA A K, KATARIA N, GAHLOT A K. Radioimmunometricquantification of serum IgE of small ruminants naturally infected withgastrointestinal worms [J]. Indian Journal of Animal Sciences,2007,77(2):136-138.
[76] SAYERS G, GOOD B, HANRAHAN J P, et al. Breed differences in mucosaland systemic antibody response to nematode infection in sheep: an important rolefor IgE?[J]. Parasitology,2008,135(1):71-80.
[77] BENDIXSEN T, EMERY D L, JONES W O. The sensitization of mucosal mastcells during infections with Trichostrongylus colubriformis or Haemonchuscontortus in sheep [J]. Int J Parasitol,1995,25(6):741-748.
[78] BISSET S A, VLASSOFF A, DOUCH P G, et al. Nematode burdens andimmunological responses following natural challenge in Romney lambsselectively bred for low or high faecal worm egg count [J]. Vet Parasitol,1996,61(3-4):249-263.
[79] CANALS A, ZARLENGA D S, ALMERIA S, et al. Cytokine profile induced bya primary infection with Ostertagia ostertagi in cattle [J]. Vet ImmunolImmunopathol,1997,58(1):63-75.
[80] ALMERIA S, CANALS A, ZARLENGA D S, et al. Quantification of cytokinegene expression in lamina propria lymphocytes of cattle following infection withOstertagia ostertagi [J]. J Parasitol,1997,83(6):1051-1055.
[81] CLAEREBOUT E, VERCAUTEREN I, GELDHOF P, et al. Cytokine responsesin immunized and non-immunized calves after Ostertagia ostertagi infection [J].Parasite Immunol,2005,27(9):325-331.
[82] DE MAREZ T, COX E, VERCRUYSSE J, et al. Identification of Ostertagiaostertagi specific cells in bovine abomasal lymph nodes [J]. Vet ImmunolImmunopathol,2000,73(2):145-154.
[83] ANTONELLI L R, DUTRA W O, OLIVEIRA R R, et al. Disparateimmunoregulatory potentials for double-negative (CD4-CD8-) alpha beta andgamma delta T cells from human patients with cutaneous leishmaniasis [J].Infect Immun,2006,74(11):6317-6323.
[84] GOMEZ-MUNOZ M T, CANALS-CABALLERO A, ALMERIA S, et al.Inhibition of bovine T lymphocyte responses by extracts of the stomach wormOstertagia ostertagi [J]. Vet Parasitol,2004,120(3):199-214.
[85] NAKAGAWA M, YOSHIHARA S, SUDA H, et al. Pathological studies onwhite spots of the liver in fattening pigs [J]. Natl Inst Anim Health Q (Tokyo),1983,23(4):138-149.
[86] ROEPSTORFF A, ERIKSEN L, SLOTVED H C, et al. Experimental Ascarissuum infection in the pig: worm population kinetics following single inoculationswith three doses of infective eggs [J]. Parasitology,1997,115(Pt4):443-452.
[87] MIQUEL N, ROEPSTORFF A, BAILEY M, et al. Host immune reactions andworm kinetics during the expulsion of Ascaris suum in pigs [J]. ParasiteImmunol,2005,27(3):79-88.
[88] ASHRAF M, URBAN J F, JR., LEE T D, et al. Characterization of isolatedporcine intestinal mucosal mast cells following infection with Ascaris suum [J].Vet Parasitol,1988,29(2-3):143-158.
[89] DAWSON H D, BESHAH E, NISHI S, et al. Localized multigene expressionpatterns support an evolving Th1/Th2-like paradigm in response to infectionswith Toxoplasma gondii and Ascaris suum [J]. Infect Immun,2005,73(2):1116-1128.
[90] USTON P I, URBAN J F, JR., ASHRAF M, et al. L3L4ES antigen andsecretagogues induce histamine release from porcine peripheral blood basophilsafter Ascaris suum infection [J]. Parasitol Res,2007,100(3):603-611.
[91] STEENHARD N R, KRINGEL H, ROEPSTORFF A, et al. Parasite-specificIL-4responses in Ascaris suum and Trichuris suis-infected pigs evaluated byELISPOT [J]. Parasite Immunol,2007,29(10):535-538.
[92] MOSER R, FEHR J, OLGIATI L, et al. Migration of primed human eosinophilsacross cytokine-activated endothelial cell monolayers [J]. Blood,1992,79(11):2937-2945.
[93] OSHIRO T M, ENOBE C S, ARAUJO C A, et al. PAS-1, a protein affinitypurified from Ascaris suum worms, maintains the ability to modulate the immuneresponse to a bystander antigen [J]. Immunol Cell Biol,2006,84(2):138-144.
[94] OSHIRO T M, MACEDO M S, MACEDO-SOARES M F. Anti-inflammatoryactivity of PAS-1, a protein component of Ascaris suum [J]. Inflamm Res,2005,54(1):17-21.
[95] SCHNIEDER T, DAUGSCHIES A. Dose-dependent pathophysiological changesin cattle experimentally infected Dictyocaulus viviparus [J]. ZentralblVeterinarmed B,1993,40(3):170-180.
[96] KNAPP N H, OAKLEY G A. Cell adherence to larvae of Dictyocaulus viviparusin vitro [J]. Res Vet Sci,1981,31(3):389-391.
[97] HAGBERG M, WATTRANG E, NISKANEN R, et al. Mononuclear cell subsetsin bronchoalveolar lavage fluid during Dictyocaulus viviparus infection of calves:a potential role for gamma/delta TCR-expressing cells in airway immuneresponses?[J]. Parasite Immunol,2005,27(5):151-161.
[98] LAHN M. The role of gamma delta T cells in the airways [J]. J Mol Med (Berl),2000,78(8):409-425.
[99] BAO S, MCCLURE S J, EMERY D L, et al. Interleukin-5mRNA expressed byeosinophils and gamma/delta T cells in parasite-immune sheep [J]. Eur JImmunol,1996,26(3):552-556.
[100] ISOGAI S, RUBIN A, MAGHNI K, et al. The effects of CD8+gamma delta Tcells on late allergic airway responses and airway inflammation in rats [J]. JAllergy Clin Immunol,2003,112(3):547-555.
[101] ISOGAI S, ATHIVIRAHAM A, FRASER R S, et al.Interferon-gamma-dependent inhibition of late allergic airway responses andeosinophilia by CD8+gamma delta T cells [J]. Immunology,2007,122(2):230-238.
[102] HAGBERG M, LUNDEN A, HOGLUND J, et al. Characterization of bovinelymphocytes stimulated in vitro by Dictyocaulus viviparus homogenate [J].Parasite Immunol,2008,30(6-7):342-353.
[103] MATTHEWS J B, DAVIDSON A J, FREEMAN K L, et al. Immunisation ofcattle with recombinant acetylcholinesterase from Dictyocaulus viviparus andwith adult worm ES products [J]. Int J Parasitol,2001,31(3):307-317.
[104] KOOYMAN F N, YATSUDA A P, PLOEGER H W, et al. Serumimmunoglobulin E response in calves infected with the lungworm Dictyocaulusviviparus and its correlation with protection [J]. Parasite Immunol,2002,24(1):47-56.
[105] JOHNSON D R, SALES J, MATTHEWS J B. Local cytokine responses inDictyocaulus viviparus infection [J]. Vet Parasitol,2005,128(3-4):309-318.
[106] SIMON F, KRAMER L H, ROMAN A, et al. Immunopathology of Dirofilariaimmitis infection [J]. Vet Res Commun,2007,31(2):161-171.
[107] SIRONI M, BANDI C, SACCHI L, et al. Molecular evidence for a closerelative of the arthropod endosymbiont Wolbachia in a filarial worm [J]. MolBiochem Parasitol,1995,74(2):223-227.
[108] TAYLOR M J, CROSS H F, BILO K. Inflammatory responses induced by thefilarial nematode Brugia malayi are mediated by lipopolysaccharide-likeactivity from endosymbiotic Wolbachia bacteria [J]. J Exp Med,2000,191(8):1429-1436.
[109] TAYLOR M J, CROSS H F, FORD L, et al. Wolbachia bacteria in filarialimmunity and disease [J]. Parasite Immunol,2001,23(7):401-409.
[110] BAZZOCCHI C, GENCHI C, PALTRINIERI S, et al. Immunological role ofthe endosymbionts of Dirofilaria immitis: the Wolbachia surface proteinactivates canine neutrophils with production of IL-8[J]. Vet Parasitol,2003,117(1-2):73-83.
[111] MARCOS-ATXUTEGI C, KRAMER L H, FERNANDEZ I, et al. Th1response in BALB/c mice immunized with Dirofilaria immitis soluble antigens:a possible role for Wolbachia?[J]. Vet Parasitol,2003,112(1-2):117-130.
[112] MEJIA J S, CARLOW C K. An analysis of the humoral immune response ofdogs following vaccination with irradiated infective larvae of Dirofilariaimmitis [J]. Parasite Immunol,1994,16(3):157-164.
[113] PRIETO G, MCCALL J W, VENCO L, et al. IgG response against infectivelarvae of Dirofilaria immitis in experimentally infected cats [J]. Vet Res,2001,32(1):93-96.
[114] TEZUKA H, IMAI S, MUTO R, et al. Recombinant Dirofilaria immitispolyprotein that stimulates murine B cells to produce nonspecific polyclonalimmunoglobulin E antibody [J]. Infect Immun,2002,70(3):1235-1244.
[115] IMAI S, TEZUKA H, FURUHASHI Y, et al. A factor of inducing IgE from afilarial parasite is an agonist of human CD40[J]. J Biol Chem,2001,276(49):46118-46124.
[116] YOSHIDA M, NAKAGAKI K, NOGAMI S, et al. Immunologic protectionagainst canine heartworm infection [J]. J Vet Med Sci,1997,59(12):1115-1121.
[117] CORBA J, ARMOUR J, ROBERTS R J, et al. Transfer of immunity toFasciola hepatica infection by lymphoid cells [J]. Res Vet Sci,1971,12(3):292-295.
[118] CLERY D, TORGERSON P, MULCAHY G. Immune responses of chronicallyinfected adult cattle to Fasciola hepatica [J]. Vet Parasitol,1996,62(1-2):71-82.
[119] HOYLE D V, TAYLOR D W. The immune response of regional lymph nodesduring the early stages of Fasciola hepatica infection in cattle [J]. ParasiteImmunol,2003,25(4):221-229.
[120] BROWN W C, DAVIS W C, DOBBELAERE D A, et al. CD4+T-cell clonesobtained from cattle chronically infected with Fasciola hepatica and specificfor adult worm antigen express both unrestricted and Th2cytokine profiles [J].Infect Immun,1994,62(3):818-827.
[121] RAADSMA H W, KINGSFORD N M, SUHARYANTA, et al. Host responsesduring experimental infection with Fasciola gigantica or Fasciola hepatica inMerino sheep I. Comparative immunological and plasma biochemical changesduring early infection [J]. Vet Parasitol,2007,143(3-4):275-286.
[122] VAN MILLIGEN F J, CORNELISSEN J B, BOKHOUT B A. Protectionagainst Fasciola hepatica in the intestine is highly correlated with eosinophiland immunoglobulin G1responses against newly excysted juveniles [J].Parasite Immunol,1999,21(5):243-251.
[123] O'BRIEN L M, FITZPATRICK E, BAIRD A W, et al. Eosinophil-nerveinteractions and neuronal plasticity in rat gut associated lymphoid tissue (GALT)in response to enteric parasitism [J]. J Neuroimmunol,2008,197(1):1-9.
[124] SERRADELL M C, GUASCONI L, CERVI L, et al. Excretory-secretoryproducts from Fasciola hepatica induce eosinophil apoptosis by acaspase-dependent mechanism [J]. Vet Immunol Immunopathol,2007,117(3-4):197-208.
[125] SERRADELL M C, GUASCONI L, MASIH D T. Involvement of amitochondrial pathway and key role of hydrogen peroxide during eosinophilapoptosis induced by excretory-secretory products from Fasciola hepatica [J].Mol Biochem Parasitol,2009,163(2):95-106.
[126] ZHANG W, MOREAU E, PEIGNE F, et al. Comparison of modulation ofsheep, mouse and buffalo lymphocyte responses by Fasciola hepatica andFasciola gigantica excretory-secretory products [J]. Parasitol Res,2005,95(5):333-338.
[127] WALSH K P, BRADY M T, FINLAY C M, et al. Infection with a helminthparasite attenuates autoimmunity through TGF-beta-mediated suppression ofTh17and Th1responses [J]. J Immunol,2009,183(3):1577-1586.
[128] SHODA L K, RICE-FICHT A C, ZHU D, et al. Bovine T cell responses torecombinant thioredoxin of Fasciola hepatica [J]. Vet Parasitol,1999,82(1):35-47.
[129] DALTON J P, NEILL S O, STACK C, et al. Fasciola hepatica cathepsin L-likeproteases: biology, function, and potential in the development of firstgeneration liver fluke vaccines [J]. Int J Parasitol,2003,33(11):1173-1181.
[130] Lightowlers MW, Gemmell MA, Harrison GLB, Heath DD, Rickard MD,Roberts MG (1992) Control of tissue parasites. II. Cestodes. In: Yong WK (ed)Animal parasite control utilizing biotechnology. CRC, Boca Raton
[131] DE ALUJA A S, VILLALOBOS A N, PLANCARTE A, et al. Taenia soliumcysticercosis: immunity in pigs induced by primary infection [J]. Vet Parasitol,1999,81(2):129-135.
[132] VERASTEGUI M, GILMAN R H, GONZALES A, et al. Taenia soliumoncosphere antigens induce immunity in pigs against experimental cysticercosis[J]. Vet Parasitol,2002,108(1):49-62.
[133] LACLETTE J P, SHOEMAKER C B, RICHTER D, et al. Paramyosin inhibitscomplement C1[J]. J Immunol,1992,148(1):124-128.
[134] BOJALIL R, TERRAZAS L I, GOVEZENSKY T, et al. Thymus-relatedcellular immune mechanisms in sex-associated resistance to experimentalmurine cysticercosis (Taenia crassiceps)[J]. J Parasitol,1993,79(3):384-389.
[135] TERRAZAS L I, BOJALIL R, GOVEZENSKY T, et al. Shift from an earlyprotective Th1-type immune response to a late permissive Th2-type response inmurine cysticercosis (Taenia crassiceps)[J]. J Parasitol,1998,84(1):74-81.
[136] ARECHAVALETA F, MOLINARI J L, TATO P. A Taenia soliummetacestode factor nonspecifically inhibits cytokine production [J]. ParasitolRes,1998,84(2):117-122.
[137] HUERTA M, DE ALUJA A S, FRAGOSO G, et al. Synthetic peptide vaccineagainst Taenia solium pig cysticercosis: successful vaccination in a controlledfield trial in rural Mexico [J]. Vaccine,2001,20(1-2):262-266.
[138] DIAZ M A, VILLALOBOS N, DE ALUJA A, et al. Th1and Th2indices of theimmune response in pigs vaccinated against Taenia solium cysticercosis suggestvarious host immune strategies against the parasite [J]. Vet ImmunolImmunopathol,2003,93(3-4):81-90.
[139] MORENO M, BENAVIDEZ U, CAROL H, et al. Local and systemic immuneresponses to Echinococcus granulosus in experimentally infected dogs [J]. VetParasitol,2004,119(1):37-50.
[140] DEPLAZES P, THOMPSON R C, CONSTANTINE C C, et al. Primaryinfection of dogs with Echinococcus granulosus: systemic and local (Peyer'spatches) immune responses [J]. Vet Immunol Immunopathol,1994,40(2):171-184.
[141] KATO N, NONAKA N, OKU Y, et al. Modified cellular immune responses indogs infected with Echinococcus multilocularis [J]. Parasitol Res,2005,95(5):339-345.
[142] BARRIGA O O, AL-KHALIDI N W. Humoral immunity in the prepatentprimary infection of dogs with Echinococcus granulosus [J]. Vet ImmunolImmunopathol,1986,11(4):375-389.
[143] AL-QAOUD K M, ABDEL-HAFEZ S K. The induction of T helper type1response by cytokine gene transfection protects mice against secondaryhydatidosis [J]. Parasitol Res,2008,102(6):1151-1155.
[144] KASSIS A I, TANNER C E. Echinococcus multilocularis: complement's role invivo in hydatid disease [J]. Exp Parasitol,1977,43(2):390-395.
[145] DIAZ A, FERREIRA A M, NIETO A. Echinococcus granulosus: interactionswith host complement in secondary infection in mice [J]. Exp Parasitol,1995,80(3):473-482.
[146] FERREIRA A M, BREIJO M, SIM R B, et al. Contribution of C5-mediatedmechanisms to host defence against Echinococcus granulosus hydatid infection[J]. Parasite Immunol,2000,22(9):445-453.
[147] MEJRI N, GOTTSTEIN B. Echinococcus multilocularis metacestodemetabolites contain a cysteine protease that digests eotaxin, a CCpro-inflammatory chemokine [J]. Parasitol Res,2009,105(5):1253-1260.
[148] HERD R P, CHAPPEL R J, BIDDELL D. Immunization of dogs againstEchinococcus granulosus using worm secretory antigens [J]. Int J Parasitol,1975,5(4):395-399.
[149] FU Y, SAINT-ANDRE MARCHAL I, MARCHAL T, et al. Cellular immuneresponse of lymph nodes from dogs following the intradermal injection of arecombinant antigen corresponding to a66kDa protein of Echinococcusgranulosus [J]. Vet Immunol Immunopathol,2000,74(3-4):195-208.
[150] ZHANG W, ZHANG Z, SHI B, et al. Vaccination of dogs againstEchinococcus granulosus, the cause of cystic hydatid disease in humans [J]. JInfect Dis,2006,194(7):966-974.
[151] WU X P, FU B Q, WANG X L, et al. Identification of antigenic genes inTrichinella spiralis by immunoscreening of cDNA libraries [J]. Vet Parasitol,2009,159(3-4):272-275.
[152]CRIADO-FORNELIO A, DE ARMAS-SERRA C, GIMENEZ-PARDO C, et al.Proteolytic enzymes from Trichinella spiralis larvae [J]. Vet Parasitol,1992,45(1-2):133-140.
[153] MOCZON T, WRANICZ M. Trichinella spiralis: proteinases in the larvae [J].Parasitol Res,1999,85(1):47-58.
[154] LIU M Y, WANG X L, FU B Q, et al. Identification of stage-specificallyexpressed genes of Trichinella spiralis by suppression subtractive hybridization[J]. Parasitology,2007,134(Pt10):1443-1455.
[155] DZIK J M. Molecules released by helminth parasites involved in hostcolonization [J]. Acta Biochim Pol,2006,53(1):33-64.
[156] ROS-MORENO R M, VAZQUEZ-LOPEZ C, GIMENEZ-PARDO C, et al. Astudy of proteases throughout the life cycle of Trichinella spiralis [J]. FoliaParasitol (Praha),2000,47(1):49-54.
[157] BALASUBRAMANIAN N, TOUBARRO D, SIMOES N. Biochemical studyand in vitro insect immune suppression by a trypsin-like secreted protease fromthe nematode Steinernema carpocapsae [J]. Parasite Immunol,2010,32(3):165-175.
[158] TODOROVA V K, STOYANOV D I. Partial characterization of serineproteinases secreted by adult Trichinella spiralis [J]. Parasitol Res,2000,86(8):684-687.
[159] TODOROVA V K. Proteolytic enzymes secreted by larval stage of the parasiticnematode Trichinella spiralis [J]. Folia Parasitol (Praha),2000,47(2):141-145.
[160] ZANG X, MAIZELS R M. Serine proteinase inhibitors from nematodes and thearms race between host and pathogen [J]. Trends Biochem Sci,2001,26(3):191-197.
[161] FRANK G R, MONDESIRE R R, BRANDT K S, et al. Antibody to theDirofilaria immitis aspartyl protease inhibitor homologue is a diagnostic markerfor feline heartworm infections [J]. J Parasitol,1998,84(6):1231-1236.
[162] ROBINSON M W, MASSIE D H, CONNOLLY B. Secretion and processing ofa novel multi-domain cystatin-like protein by intracellular stages of Trichinellaspiralis [J]. Mol Biochem Parasitol,2007,151(1):9-17.
[163] MAIZELS R M, GOMEZ-ESCOBAR N, GREGORY W F, et al. Immuneevasion genes from filarial nematodes [J]. Int J Parasitol,2001,31(9):889-898.
[164] YANG Y, ZHANG Z, YANG J, et al. Oral vaccination with Ts87DNA vaccinedelivered by attenuated Salmonella typhimurium elicits a protective immuneresponse against Trichinella spiralis larval challenge [J]. Vaccine,2010,28(15):2735-2742.
[165] WEI J, GU Y, YANG J, et al. Identification and characterization of protectiveepitope of Trichinella spiralis paramyosin [J]. Vaccine,2011,29(17):3162-3168.
[166] HEIN W R, HARRISON G B. Vaccines against veterinary helminths [J]. VetParasitol,2005,132(3-4):217-222.
[167]于申业.高质量基因重组蛋白在屠宰动物旋毛虫病诊断中的应用[D].吉林：吉林大学畜牧兽医学院，2009.
[168] FENG S, WU X, WANG X, et al. Vaccination of Mice with an AntigenicSerine Protease-Like Protein Elicits a Protective Immune Response againstTrichinella Spiralis Infection [J]. J Parasitol,2012,
[169] JONES M K, GOBERT G N, ZHANG L, et al. The cytoskeleton and motorproteins of human schistosomes and their roles in surface maintenance andhost-parasite interactions [J]. Bioessays,2004,26(7):752-765.
[170] VAN HELLEMOND J J, RETRA K, BROUWERS J F, et al. Functions of thetegument of schistosomes: clues from the proteome and lipidome [J]. Int JParasitol,2006,36(6):691-699.
[171] LIGAS J A, KEREPESI L A, GALIOTO A M, et al. Specificity andmechanism of immunoglobulin M (IgM)-and IgG-dependent protectiveimmunity to larval Strongyloides stercoralis in mice [J]. Infect Immun,2003,71(12):6835-6843.
[172] KEREPESI L A, NOLAN T J, SCHAD G A, et al. Human immunoglobulin Gmediates protective immunity and identifies protective antigens against larvalStrongyloides stercoralis in mice [J]. J Infect Dis,2004,189(7):1282-1290.
[173] GALIOTO A M, HESS J A, NOLAN T J, et al. Role of eosinophils andneutrophils in innate and adaptive protective immunity to larval strongyloidesstercoralis in mice [J]. Infect Immun,2006,74(10):5730-5738.
[174] BRIGANDI R A, ROTMAN H L, YUTANAWIBOONCHAI W, et al.Strongyloides stercoralis: role of antibody and complement in immunity to thethird stage of larvae in BALB/c ByJ mice [J]. Exp Parasitol,1996,82(3):279-289.
[175] KEREPESI L A, HESS J A, NOLAN T J, et al. Complement component C3isrequired for protective innate and adaptive immunity to larval strongyloidesstercoralis in mice [J]. J Immunol,2006,176(7):4315-4322.
[176] HARRIS N, GAUSE W C. To B or not to B: B cells and the Th2-type immuneresponse to helminths [J]. Trends Immunol,2011,32(2):80-88.
[177] DIEMERT D J, BETHONY J M, HOTEZ P J. Hookworm vaccines [J]. ClinInfect Dis,2008,46(2):282-288.
[178] MCMANUS D P, LOUKAS A. Current status of vaccines for schistosomiasis[J]. Clin Microbiol Rev,2008,21(1):225-242.
[179] KOLODZIEJ-SOBOCINSKA M, DVOROZNAKOVA E, DZIEMIAN E.Trichinella spiralis: macrophage activity and antibody response in chronicmurine infection [J]. Exp Parasitol,2006,112(1):52-62.
[180] GIULIETTI A, OVERBERGH L, VALCKX D, et al. An overview of real-timequantitative PCR: applications to quantify cytokine gene expression [J].Methods,2001,25(4):386-401.
[181] ZAROS L G, BRICARELLO P A, AMARANTE A F T, et al. Quantification ofbovine. cytokine gene expression using real-time RT-PCR methodology [J].Genetics and Molecular Biology,2007,30(3):575-579.
[182] FOSTER N, ELSHEIKHA H M. The immune response to parasitic helminthsof veterinary importance and its potential manipulation for future vaccinecontrol strategies [J]. Parasitol Res,2012,110(5):1587-1599.
[183] BRUSCHI F, CHIUMIENTO L. Immunomodulation in trichinellosis: doesTrichinella really escape the host immune system?[J]. Endocr Metab ImmuneDisord Drug Targets,2012,12(1):4-15.
[184] PATEL N, KREIDER T, URBAN J F, JR., et al. Characterisation of effectormechanisms at the host:parasite interface during the immune response totissue-dwelling intestinal nematode parasites [J]. Int J Parasitol,2009,39(1):13-21.
[185] SCHOPF L R, HOFFMANN K F, CHEEVER A W, et al. IL-10is critical forhost resistance and survival during gastrointestinal helminth infection [J]. JImmunol,2002,168(5):2383-2392.
[186] LIGHTOWLERS M W, COLEBROOK A L, GAUCI C G, et al. Vaccinationagainst cestode parasites: anti-helminth vaccines that work and why [J]. VetParasitol,2003,115(2):83-123.
[187] DZIADEK B, GATKOWSKA J, BRZOSTEK A, et al. Evaluation of threerecombinant multi-antigenic vaccines composed of surface and secretoryantigens of Toxoplasma gondii in murine models of experimentaltoxoplasmosis [J]. Vaccine,2011,29(4):821-830.
[188] HALASSY B, VDOVIC V, HABJANEC L, et al. Effectiveness of novelPGM-containing incomplete Seppic adjuvants in rabbits [J]. Vaccine,2007,25(17):3475-3481.
[189] AGUADO T, ENGERS H, PANG T, et al. Novel adjuvants currently in clinicaltesting November2-4,1998, Fondation Merieux, Annecy, France: a meetingsponsored by the World Health Organization [J]. Vaccine,1999,17(19):2321-2328.
[190] HUI G S, HASHIMOTO C N. Pathways for potentiation of immunogenicityduring adjuvant-assisted immunizations with Plasmodium falciparum majormerozoite surface protein1[J]. Infect Immun,1998,66(11):5329-5336.
[191] SACHDEVA S, MOHMMED A, DASARADHI P V, et al. Immunogenicityand protective efficacy of Escherichia coli expressed Plasmodium falciparummerozoite surface protein-1(42) using human compatible adjuvants [J]. Vaccine,2006,24(12):2007-2016.
[192] GUPTA R K. Aluminum compounds as vaccine adjuvants [J]. Adv Drug DelivRev,1998,32(3):155-172.
[2] BIOREAU P, VAYSSIER M, FABIEN J F, et al. Characterization of elevenantigenic groups in Trichinella genus and identification of stage and speciesmarkers [J]. Parasitology,1997,115(Pt6):641-651.
[3] DEVILLE S, POOTER A, AUCOUTURIER J, et al. Influence of adjuvantformulation on the induced protection of mice immunized with total solubleantigen of Trichinella spiralis [J]. Vet Parasitol,2005,132(1-2):75-80.
[4] LIGHTOWLERS M W. Cestode vaccines: origins, current status and futureprospects [J]. Parasitology,2006,133Suppl: S27-42.
[5] LUSTIGMAN S, JAMES E R, TAWE W, et al. Towards a recombinant antigenvaccine against Onchocerca volvulus [J]. Trends Parasitol,2002,18(3):135-141.
[6] TRAP C, FU B, LE GUERHIER F, et al. Cloning and analysis of a cDNAencoding a putative serine protease comprising two trypsin-like domains ofTrichinella spiralis [J]. Parasitol Res,2006,98(4):288-294.
[7] ALLEN J E, MAIZELS R M. Diversity and dialogue in immunity to helminths[J]. Nat Rev Immunol,2011,11(6):375-388.
[8] MATISZ C E, MCDOUGALL J J, SHARKEY K A, et al. Helminth parasitesand the modulation of joint inflammation [J]. J Parasitol Res,2011,2011(942616).
[9] FLEMING J O. Helminths and multiple sclerosis: will old friends give us newtreatments for MS?[J]. J Neuroimmunol,2011,233(1-2):3-5.
[10] FLEMING J O, ISAAK A, LEE J E, et al. Probiotic helminth administration inrelapsing-remitting multiple sclerosis: a phase1study [J]. Mult Scler,2011,17(6):743-754.
[11] HE Y, LI J, ZHUANG W, et al. The inhibitory effect against collagen-inducedarthritis by Schistosoma japonicum infection is infection stage-dependent [J].BMC Immunol,2010,11(28).
[12] MCKAY D M. The therapeutic helminth?[J]. Trends Parasitol,2009,25(3):109-114.
[13] REIS E SOUSA C, HIENY S, SCHARTON-KERSTEN T, et al. In vivomicrobial stimulation induces rapid CD40ligand-independent production ofinterleukin12by dendritic cells and their redistribution to T cell areas [J]. J ExpMed,1997,186(11):1819-1829.
[14] MAIZELS R M, BALIC A, GOMEZ-ESCOBAR N, et al. Helminthparasites--masters of regulation [J]. Immunol Rev,2004,201:89-116.
[15] VAN RIET E, EVERTS B, RETRA K, et al. Combined TLR2and TLR4ligationin the context of bacterial or helminth extracts in human monocyte deriveddendritic cells: molecular correlates for Th1/Th2polarization [J]. BMC Immunol,2009,10(9).
[16] CERVI L, MACDONALD A S, KANE C, et al. Cutting edge: dendritic cellscopulsed with microbial and helminth antigens undergo modified maturation,segregate the antigens to distinct intracellular compartments, and concurrentlyinduce microbe-specific Th1and helminth-specific Th2responses [J]. J Immunol,2004,172(4):2016-2020.
[17] WHELAN M, HARNETT M M, HOUSTON K M, et al. A filarialnematode-secreted product signals dendritic cells to acquire a phenotype thatdrives development of Th2cells [J]. J Immunol,2000,164(12):6453-6460.
[18] BALIC A, HARCUS Y, HOLLAND M J, et al. Selective maturation of dendriticcells by Nippostrongylus brasiliensis-secreted proteins drives Th2immuneresponses [J]. Eur J Immunol,2004,34(11):3047-3059.
[19] GRAINGER J R, SMITH K A, HEWITSON J P, et al. Helminth secretionsinduce de novo T cell Foxp3expression and regulatory function through theTGF-beta pathway [J]. J Exp Med,2010,207(11):2331-2341.
[20] BEITING D P, GAGLIARDO L F, HESSE M, et al. Coordinated control ofimmunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, andTGF-beta [J]. J Immunol,2007,178(2):1039-1047.
[21] WU Z, SOFRONIC-MILOSAVLJEVIC L, NAGANO I, et al. Trichinellaspiralis: nurse cell formation with emphasis on analogy to muscle cell repair [J].Parasit Vectors,2008,1(1):27.
[22] NAGANO I, WU Z, TAKAHASHI Y. Functional genes and proteins ofTrichinella spp [J]. Parasitol Res,2009,104(2):197-207.
[23] ELSE K J. Have gastrointestinal nematodes outwitted the immune system?[J].Parasite Immunol,2005,27(10-11):407-415.
[24] MOSMANN T R. Cytokine secretion patterns and cross-regulation of T cellsubsets [J]. Immunol Res,1991,10(3-4):183-188.
[25] ISHIKAWA N, GOYAL P K, MAHIDA Y R, et al. Early cytokine responsesduring intestinal parasitic infections [J]. Immunology,1998,93(2):257-263.
[26] FINNEY C A, TAYLOR M D, WILSON M S, et al. Expansion and activation ofCD4+CD25+regulatory T cells in Heligmosomoides polygyrus infection [J]. EurJ Immunol,2007,37(7):1874-1886.
[27] TAYLOR J J, MOHRS M, PEARCE E J. Regulatory T cell responses develop inparallel to Th responses and control the magnitude and phenotype of the Theffector population [J]. J Immunol,2006,176(10):5839-5847.
[28] SHER A, PEARCE E, KAYE P. Shaping the immune response to parasites: roleof dendritic cells [J]. Curr Opin Immunol,2003,15(4):421-429.
[29] KANE C M, CERVI L, SUN J, et al. Helminth antigens modulate TLR-initiateddendritic cell activation [J]. J Immunol,2004,173(12):7454-7461.
[30] SEGURA M, SU Z, PICCIRILLO C, et al. Impairment of dendritic cell functionby excretory-secretory products: a potential mechanism for nematode-inducedimmunosuppression [J]. Eur J Immunol,2007,37(7):1887-1904.
[31] VAN RIET E, HARTGERS F C, YAZDANBAKHSH M. Chronic helminthinfections induce immunomodulation: consequences and mechanisms [J].Immunobiology,2007,212(6):475-490.
[32] MACDONALD A S, MAIZELS R M. Alarming dendritic cells for Th2induction [J]. J Exp Med,2008,205(1):13-17.
[33] ILIC N, GRUDEN-MOVSESIJAN A, SOFRONIC-MILOSAVLJEVIC L.Trichinella spiralis: shaping the immune response [J]. Immunol Res,2012,52(1-2):111-119.
[34] ILIC N, WORTHINGTON J J, GRUDEN-MOVSESIJAN A, et al. Trichinellaspiralis antigens prime mixed Th1/Th2response but do not induce de novogeneration of Foxp3+T cells in vitro [J]. Parasite Immunol,2011,33(10):572-582.
[35] ILIC N, COLIC M, GRUDEN-MOVSESIJAN A, et al. Characterization of ratbone marrow dendritic cells initially primed by Trichinella spiralis antigens [J].Parasite Immunol,2008,30(9):491-495.
[36] LEECH M D, GRENCIS R K. Induction of enhanced immunity to intestinalnematodes using IL-9-producing dendritic cells [J]. J Immunol,2006,176(4):2505-2511.
[37] LANGELAAR M, ARANZAMENDI C, FRANSSEN F, et al. Suppression ofdendritic cell maturation by Trichinella spiralis excretory/secretory products [J].Parasite Immunol,2009,31(10):641-645.
[38] THOMAS P G, CARTER M R, ATOCHINA O, et al. Maturation of dendriticcell2phenotype by a helminth glycan uses a Toll-like receptor4-dependentmechanism [J]. J Immunol,2003,171(11):5837-5841.
[39] JENKINS S J, MOUNTFORD A P. Dendritic cells activated with productsreleased by schistosome larvae drive Th2-type immune responses, which can beinhibited by manipulation of CD40costimulation [J]. Infect Immun,2005,73(1):395-402.
[40] MARSHALL F A, PEARCE E J. Uncoupling of induced protein processingfrom maturation in dendritic cells exposed to a highly antigenic preparation froma helminth parasite [J]. J Immunol,2008,181(11):7562-7570.
[41] PONCINI C V, ALBA SOTO C D, BATALLA E, et al. Trypanosoma cruziinduces regulatory dendritic cells in vitro [J]. Infect Immun,2008,76(6):2633-2641.
[42] BOUSHERI S, CAO H. New insight into the role of dendritic cells in malariaimmune pathogenesis [J]. Trends Parasitol,2008,24(5):199-200.
[43] REVEST M, DONAGHY L, CABILLIC F, et al. Comparison of theimmunomodulatory effects of L. donovani and L. major excreted-secretedantigens, particulate and soluble extracts and viable parasites on human dendriticcells [J]. Vaccine,2008,26(48):6119-6123.
[44] WIETHE C, DEBUS A, MOHRS M, et al. Dendritic cell differentiation state andtheir interaction with NKT cells determine Th1/Th2differentiation in the murinemodel of Leishmania major infection [J]. J Immunol,2008,180(7):4371-4381.
[45] MANICKASINGHAM S P, EDWARDS A D, SCHULZ O, et al. The ability ofmurine dendritic cell subsets to direct T helper cell differentiation is dependenton microbial signals [J]. Eur J Immunol,2003,33(1):101-107.
[46] CHANG J, KUNKEL S L, CHANG C H. Negative regulation ofMyD88-dependent signaling by IL-10in dendritic cells [J]. Proc Natl Acad Sci US A,2009,106(43):18327-18332.
[47] XIA C Q, KAO K J. Suppression of interleukin-12production throughendogenously secreted interleukin-10in activated dendritic cells: involvement ofactivation of extracellular signal-regulated protein kinase [J]. Scand J Immunol,2003,58(1):23-32.
[48] MUTHANA M, FAIRBURN B, MIRZA S, et al. Identification of a rat bonemarrow-derived dendritic cell population which secretes both IL-10and IL-12:evidence against a reciprocal relationship between IL-10and IL-12secretion [J].Immunobiology,2006,211(5):391-402.
[49] SALLUSTO F, LANZAVECCHIA A. The instructive role of dendritic cells onT-cell responses [J]. Arthritis Res,2002,4Suppl3: S127-132.
[50] CARVALHO L P, PEARCE E J, SCOTT P. Functional dichotomy of dendriticcells following interaction with Leishmania braziliensis: infected cells producehigh levels of TNF-alpha, whereas bystander dendritic cells are activated topromote T cell responses [J]. J Immunol,2008,181(9):6473-6480.
[51] VASQUEZ R E, XIN L, SOONG L. Effects of CXCL10on dendritic cell andCD4+T-cell functions during Leishmania amazonensis infection [J]. InfectImmun,2008,76(1):161-169.
[52] SHAW J, GRUND V, DURLING L, et al. Dendritic cells pulsed with arecombinant chlamydial major outer membrane protein antigen elicit a CD4+type2rather than type1immune response that is not protective [J]. InfectImmun,2002,70(3):1097-1105.
[53] KOYASU S, MORO K, TANABE M, et al. Natural helper cells: a new player inthe innate immune response against helminth infection [J]. Adv Immunol,2010,108:21-44.
[54] SAENZ S A, NOTI M, ARTIS D. Innate immune cell populations function asinitiators and effectors in Th2cytokine responses [J]. Trends Immunol,2010,31(11):407-413.
[55] MACDONALD A S, ARAUJO M I, PEARCE E J. Immunology of parasitichelminth infections [J]. Infect Immun,2002,70(2):427-433.
[56] GRUDEN-MOVSESIJAN A, ILIC N, COLIC M, et al. The impact ofTrichinella spiralis excretory-secretory products on dendritic cells [J]. CompImmunol Microbiol Infect Dis,2011,34(5):429-439.
[57] GRUDEN-MOVSESIJAN A, ILIC N, MOSTARICA-STOJKOVIC M, et al.Mechanisms of modulation of experimental autoimmune encephalomyelitis bychronic Trichinella spiralis infection in Dark Agouti rats [J]. Parasite Immunol,2010,32(6):450-459.
[58] MALDONADO R A, VON ANDRIAN U H. How tolerogenic dendritic cellsinduce regulatory T cells [J]. Adv Immunol,2010,108:111-165.
[59] BABU S, BLAUVELT C P, KUMARASWAMI V, et al. Regulatory networksinduced by live parasites impair both Th1and Th2pathways in patent lymphaticfilariasis: implications for parasite persistence [J]. J Immunol,2006,176(5):3248-3256.
[60] SAKAGUCHI S, ONO M, SETOGUCHI R, et al. Foxp3+CD25+CD4+naturalregulatory T cells in dominant self-tolerance and autoimmune disease [J].Immunol Rev,2006,212:8-27.
[61] SUTHERLAND I A, LEATHWICK D M. Anthelmintic resistance in nematodeparasites of cattle: a global issue?[J]. Trends Parasitol,2011,27(4):176-181.
[62] HOSTE H, TORRES-ACOSTA J F. Non chemical control of helminths inruminants: adapting solutions for changing worms in a changing world [J]. VetParasitol,2011,180(1-2):144-154.
[63] CLAEREBOUT E, KNOX D P, VERCRUYSSE J. Current research and futureprospects in the development of vaccines against gastrointestinal nematodes incattle [J]. Expert Rev Vaccines,2003,2(1):147-157.
[64] MEEUSEN E N, PIEDRAFITA D. Exploiting natural immunity to helminthparasites for the development of veterinary vaccines [J]. Int J Parasitol,2003,33(11):1285-1290.
[65] VERCRUYSSE J, KNOX D P, SCHETTERS T P, et al. Veterinary parasiticvaccines: pitfalls and future directions [J]. Trends Parasitol,2004,20(10):488-492.
[66] SMITH W D, ZARLENGA D S. Developments and hurdles in generatingvaccines for controlling helminth parasites of grazing ruminants [J]. Vet Parasitol,2006,139(4):347-359.
[67] BISSET S A, MORRIS C A, MCEWAN J C, et al. Breeding sheep in NewZealand that are less reliant on anthelmintics to maintain health and productivity[J]. N Z Vet J,2001,49(6):236-246.
[68] URBAN J F, JR., KATONA I M, PAUL W E, et al. Interleukin4is important inprotective immunity to a gastrointestinal nematode infection in mice [J]. ProcNatl Acad Sci U S A,1991,88(13):5513-5517.
[69] FINKELMAN F D, MADDEN K B, CHEEVER A W, et al. Effects ofinterleukin12on immune responses and host protection in mice infected withintestinal nematode parasites [J]. J Exp Med,1994,179(5):1563-1572.
[70] SHAKYA K P, MILLER J E, HOROHOV D W. A Th2type of immuneresponse is associated with increased resistance to Haemonchus contortus innaturally infected Gulf Coast Native lambs [J]. Vet Parasitol,2009,163(1-2):57-66.
[71] RAINBIRD M A, MACMILLAN D, MEEUSEN E N. Eosinophil-mediatedkilling of Haemonchus contortus larvae: effect of eosinophil activation and roleof antibody, complement and interleukin-5[J]. Parasite Immunol,1998,20(2):93-103.
[72] BALIC A, BOWLES V M, MEEUSEN E N. Mechanisms of immunity toHaemonchus contortus infection in sheep [J]. Parasite Immunol,2002,24(1):39-46.
[73] BALIC A, CUNNINGHAM C P, MEEUSEN E N. Eosinophil interactions withHaemonchus contortus larvae in the ovine gastrointestinal tract [J]. ParasiteImmunol,2006,28(3):107-115.
[74] SHAW R, PFEFFER A, BISCHOF R. Ovine IgE and its role in immunologicalprotection and disease [J]. Vet Immunol Immunopathol,2009,132(1):31-40.
[75] KATARIA A K, KATARIA N, GAHLOT A K. Radioimmunometricquantification of serum IgE of small ruminants naturally infected withgastrointestinal worms [J]. Indian Journal of Animal Sciences,2007,77(2):136-138.
[76] SAYERS G, GOOD B, HANRAHAN J P, et al. Breed differences in mucosaland systemic antibody response to nematode infection in sheep: an important rolefor IgE?[J]. Parasitology,2008,135(1):71-80.
[77] BENDIXSEN T, EMERY D L, JONES W O. The sensitization of mucosal mastcells during infections with Trichostrongylus colubriformis or Haemonchuscontortus in sheep [J]. Int J Parasitol,1995,25(6):741-748.
[78] BISSET S A, VLASSOFF A, DOUCH P G, et al. Nematode burdens andimmunological responses following natural challenge in Romney lambsselectively bred for low or high faecal worm egg count [J]. Vet Parasitol,1996,61(3-4):249-263.
[79] CANALS A, ZARLENGA D S, ALMERIA S, et al. Cytokine profile induced bya primary infection with Ostertagia ostertagi in cattle [J]. Vet ImmunolImmunopathol,1997,58(1):63-75.
[80] ALMERIA S, CANALS A, ZARLENGA D S, et al. Quantification of cytokinegene expression in lamina propria lymphocytes of cattle following infection withOstertagia ostertagi [J]. J Parasitol,1997,83(6):1051-1055.
[81] CLAEREBOUT E, VERCAUTEREN I, GELDHOF P, et al. Cytokine responsesin immunized and non-immunized calves after Ostertagia ostertagi infection [J].Parasite Immunol,2005,27(9):325-331.
[82] DE MAREZ T, COX E, VERCRUYSSE J, et al. Identification of Ostertagiaostertagi specific cells in bovine abomasal lymph nodes [J]. Vet ImmunolImmunopathol,2000,73(2):145-154.
[83] ANTONELLI L R, DUTRA W O, OLIVEIRA R R, et al. Disparateimmunoregulatory potentials for double-negative (CD4-CD8-) alpha beta andgamma delta T cells from human patients with cutaneous leishmaniasis [J].Infect Immun,2006,74(11):6317-6323.
[84] GOMEZ-MUNOZ M T, CANALS-CABALLERO A, ALMERIA S, et al.Inhibition of bovine T lymphocyte responses by extracts of the stomach wormOstertagia ostertagi [J]. Vet Parasitol,2004,120(3):199-214.
[85] NAKAGAWA M, YOSHIHARA S, SUDA H, et al. Pathological studies onwhite spots of the liver in fattening pigs [J]. Natl Inst Anim Health Q (Tokyo),1983,23(4):138-149.
[86] ROEPSTORFF A, ERIKSEN L, SLOTVED H C, et al. Experimental Ascarissuum infection in the pig: worm population kinetics following single inoculationswith three doses of infective eggs [J]. Parasitology,1997,115(Pt4):443-452.
[87] MIQUEL N, ROEPSTORFF A, BAILEY M, et al. Host immune reactions andworm kinetics during the expulsion of Ascaris suum in pigs [J]. ParasiteImmunol,2005,27(3):79-88.
[88] ASHRAF M, URBAN J F, JR., LEE T D, et al. Characterization of isolatedporcine intestinal mucosal mast cells following infection with Ascaris suum [J].Vet Parasitol,1988,29(2-3):143-158.
[89] DAWSON H D, BESHAH E, NISHI S, et al. Localized multigene expressionpatterns support an evolving Th1/Th2-like paradigm in response to infectionswith Toxoplasma gondii and Ascaris suum [J]. Infect Immun,2005,73(2):1116-1128.
[90] USTON P I, URBAN J F, JR., ASHRAF M, et al. L3L4ES antigen andsecretagogues induce histamine release from porcine peripheral blood basophilsafter Ascaris suum infection [J]. Parasitol Res,2007,100(3):603-611.
[91] STEENHARD N R, KRINGEL H, ROEPSTORFF A, et al. Parasite-specificIL-4responses in Ascaris suum and Trichuris suis-infected pigs evaluated byELISPOT [J]. Parasite Immunol,2007,29(10):535-538.
[92] MOSER R, FEHR J, OLGIATI L, et al. Migration of primed human eosinophilsacross cytokine-activated endothelial cell monolayers [J]. Blood,1992,79(11):2937-2945.
[93] OSHIRO T M, ENOBE C S, ARAUJO C A, et al. PAS-1, a protein affinitypurified from Ascaris suum worms, maintains the ability to modulate the immuneresponse to a bystander antigen [J]. Immunol Cell Biol,2006,84(2):138-144.
[94] OSHIRO T M, MACEDO M S, MACEDO-SOARES M F. Anti-inflammatoryactivity of PAS-1, a protein component of Ascaris suum [J]. Inflamm Res,2005,54(1):17-21.
[95] SCHNIEDER T, DAUGSCHIES A. Dose-dependent pathophysiological changesin cattle experimentally infected Dictyocaulus viviparus [J]. ZentralblVeterinarmed B,1993,40(3):170-180.
[96] KNAPP N H, OAKLEY G A. Cell adherence to larvae of Dictyocaulus viviparusin vitro [J]. Res Vet Sci,1981,31(3):389-391.
[97] HAGBERG M, WATTRANG E, NISKANEN R, et al. Mononuclear cell subsetsin bronchoalveolar lavage fluid during Dictyocaulus viviparus infection of calves:a potential role for gamma/delta TCR-expressing cells in airway immuneresponses?[J]. Parasite Immunol,2005,27(5):151-161.
[98] LAHN M. The role of gamma delta T cells in the airways [J]. J Mol Med (Berl),2000,78(8):409-425.
[99] BAO S, MCCLURE S J, EMERY D L, et al. Interleukin-5mRNA expressed byeosinophils and gamma/delta T cells in parasite-immune sheep [J]. Eur JImmunol,1996,26(3):552-556.
[100] ISOGAI S, RUBIN A, MAGHNI K, et al. The effects of CD8+gamma delta Tcells on late allergic airway responses and airway inflammation in rats [J]. JAllergy Clin Immunol,2003,112(3):547-555.
[101] ISOGAI S, ATHIVIRAHAM A, FRASER R S, et al.Interferon-gamma-dependent inhibition of late allergic airway responses andeosinophilia by CD8+gamma delta T cells [J]. Immunology,2007,122(2):230-238.
[102] HAGBERG M, LUNDEN A, HOGLUND J, et al. Characterization of bovinelymphocytes stimulated in vitro by Dictyocaulus viviparus homogenate [J].Parasite Immunol,2008,30(6-7):342-353.
[103] MATTHEWS J B, DAVIDSON A J, FREEMAN K L, et al. Immunisation ofcattle with recombinant acetylcholinesterase from Dictyocaulus viviparus andwith adult worm ES products [J]. Int J Parasitol,2001,31(3):307-317.
[104] KOOYMAN F N, YATSUDA A P, PLOEGER H W, et al. Serumimmunoglobulin E response in calves infected with the lungworm Dictyocaulusviviparus and its correlation with protection [J]. Parasite Immunol,2002,24(1):47-56.
[105] JOHNSON D R, SALES J, MATTHEWS J B. Local cytokine responses inDictyocaulus viviparus infection [J]. Vet Parasitol,2005,128(3-4):309-318.
[106] SIMON F, KRAMER L H, ROMAN A, et al. Immunopathology of Dirofilariaimmitis infection [J]. Vet Res Commun,2007,31(2):161-171.
[107] SIRONI M, BANDI C, SACCHI L, et al. Molecular evidence for a closerelative of the arthropod endosymbiont Wolbachia in a filarial worm [J]. MolBiochem Parasitol,1995,74(2):223-227.
[108] TAYLOR M J, CROSS H F, BILO K. Inflammatory responses induced by thefilarial nematode Brugia malayi are mediated by lipopolysaccharide-likeactivity from endosymbiotic Wolbachia bacteria [J]. J Exp Med,2000,191(8):1429-1436.
[109] TAYLOR M J, CROSS H F, FORD L, et al. Wolbachia bacteria in filarialimmunity and disease [J]. Parasite Immunol,2001,23(7):401-409.
[110] BAZZOCCHI C, GENCHI C, PALTRINIERI S, et al. Immunological role ofthe endosymbionts of Dirofilaria immitis: the Wolbachia surface proteinactivates canine neutrophils with production of IL-8[J]. Vet Parasitol,2003,117(1-2):73-83.
[111] MARCOS-ATXUTEGI C, KRAMER L H, FERNANDEZ I, et al. Th1response in BALB/c mice immunized with Dirofilaria immitis soluble antigens:a possible role for Wolbachia?[J]. Vet Parasitol,2003,112(1-2):117-130.
[112] MEJIA J S, CARLOW C K. An analysis of the humoral immune response ofdogs following vaccination with irradiated infective larvae of Dirofilariaimmitis [J]. Parasite Immunol,1994,16(3):157-164.
[113] PRIETO G, MCCALL J W, VENCO L, et al. IgG response against infectivelarvae of Dirofilaria immitis in experimentally infected cats [J]. Vet Res,2001,32(1):93-96.
[114] TEZUKA H, IMAI S, MUTO R, et al. Recombinant Dirofilaria immitispolyprotein that stimulates murine B cells to produce nonspecific polyclonalimmunoglobulin E antibody [J]. Infect Immun,2002,70(3):1235-1244.
[115] IMAI S, TEZUKA H, FURUHASHI Y, et al. A factor of inducing IgE from afilarial parasite is an agonist of human CD40[J]. J Biol Chem,2001,276(49):46118-46124.
[116] YOSHIDA M, NAKAGAKI K, NOGAMI S, et al. Immunologic protectionagainst canine heartworm infection [J]. J Vet Med Sci,1997,59(12):1115-1121.
[117] CORBA J, ARMOUR J, ROBERTS R J, et al. Transfer of immunity toFasciola hepatica infection by lymphoid cells [J]. Res Vet Sci,1971,12(3):292-295.
[118] CLERY D, TORGERSON P, MULCAHY G. Immune responses of chronicallyinfected adult cattle to Fasciola hepatica [J]. Vet Parasitol,1996,62(1-2):71-82.
[119] HOYLE D V, TAYLOR D W. The immune response of regional lymph nodesduring the early stages of Fasciola hepatica infection in cattle [J]. ParasiteImmunol,2003,25(4):221-229.
[120] BROWN W C, DAVIS W C, DOBBELAERE D A, et al. CD4+T-cell clonesobtained from cattle chronically infected with Fasciola hepatica and specificfor adult worm antigen express both unrestricted and Th2cytokine profiles [J].Infect Immun,1994,62(3):818-827.
[121] RAADSMA H W, KINGSFORD N M, SUHARYANTA, et al. Host responsesduring experimental infection with Fasciola gigantica or Fasciola hepatica inMerino sheep I. Comparative immunological and plasma biochemical changesduring early infection [J]. Vet Parasitol,2007,143(3-4):275-286.
[122] VAN MILLIGEN F J, CORNELISSEN J B, BOKHOUT B A. Protectionagainst Fasciola hepatica in the intestine is highly correlated with eosinophiland immunoglobulin G1responses against newly excysted juveniles [J].Parasite Immunol,1999,21(5):243-251.
[123] O'BRIEN L M, FITZPATRICK E, BAIRD A W, et al. Eosinophil-nerveinteractions and neuronal plasticity in rat gut associated lymphoid tissue (GALT)in response to enteric parasitism [J]. J Neuroimmunol,2008,197(1):1-9.
[124] SERRADELL M C, GUASCONI L, CERVI L, et al. Excretory-secretoryproducts from Fasciola hepatica induce eosinophil apoptosis by acaspase-dependent mechanism [J]. Vet Immunol Immunopathol,2007,117(3-4):197-208.
[125] SERRADELL M C, GUASCONI L, MASIH D T. Involvement of amitochondrial pathway and key role of hydrogen peroxide during eosinophilapoptosis induced by excretory-secretory products from Fasciola hepatica [J].Mol Biochem Parasitol,2009,163(2):95-106.
[126] ZHANG W, MOREAU E, PEIGNE F, et al. Comparison of modulation ofsheep, mouse and buffalo lymphocyte responses by Fasciola hepatica andFasciola gigantica excretory-secretory products [J]. Parasitol Res,2005,95(5):333-338.
[127] WALSH K P, BRADY M T, FINLAY C M, et al. Infection with a helminthparasite attenuates autoimmunity through TGF-beta-mediated suppression ofTh17and Th1responses [J]. J Immunol,2009,183(3):1577-1586.
[128] SHODA L K, RICE-FICHT A C, ZHU D, et al. Bovine T cell responses torecombinant thioredoxin of Fasciola hepatica [J]. Vet Parasitol,1999,82(1):35-47.
[129] DALTON J P, NEILL S O, STACK C, et al. Fasciola hepatica cathepsin L-likeproteases: biology, function, and potential in the development of firstgeneration liver fluke vaccines [J]. Int J Parasitol,2003,33(11):1173-1181.
[130] Lightowlers MW, Gemmell MA, Harrison GLB, Heath DD, Rickard MD,Roberts MG (1992) Control of tissue parasites. II. Cestodes. In: Yong WK (ed)Animal parasite control utilizing biotechnology. CRC, Boca Raton
[131] DE ALUJA A S, VILLALOBOS A N, PLANCARTE A, et al. Taenia soliumcysticercosis: immunity in pigs induced by primary infection [J]. Vet Parasitol,1999,81(2):129-135.
[132] VERASTEGUI M, GILMAN R H, GONZALES A, et al. Taenia soliumoncosphere antigens induce immunity in pigs against experimental cysticercosis[J]. Vet Parasitol,2002,108(1):49-62.
[133] LACLETTE J P, SHOEMAKER C B, RICHTER D, et al. Paramyosin inhibitscomplement C1[J]. J Immunol,1992,148(1):124-128.
[134] BOJALIL R, TERRAZAS L I, GOVEZENSKY T, et al. Thymus-relatedcellular immune mechanisms in sex-associated resistance to experimentalmurine cysticercosis (Taenia crassiceps)[J]. J Parasitol,1993,79(3):384-389.
[135] TERRAZAS L I, BOJALIL R, GOVEZENSKY T, et al. Shift from an earlyprotective Th1-type immune response to a late permissive Th2-type response inmurine cysticercosis (Taenia crassiceps)[J]. J Parasitol,1998,84(1):74-81.
[136] ARECHAVALETA F, MOLINARI J L, TATO P. A Taenia soliummetacestode factor nonspecifically inhibits cytokine production [J]. ParasitolRes,1998,84(2):117-122.
[137] HUERTA M, DE ALUJA A S, FRAGOSO G, et al. Synthetic peptide vaccineagainst Taenia solium pig cysticercosis: successful vaccination in a controlledfield trial in rural Mexico [J]. Vaccine,2001,20(1-2):262-266.
[138] DIAZ M A, VILLALOBOS N, DE ALUJA A, et al. Th1and Th2indices of theimmune response in pigs vaccinated against Taenia solium cysticercosis suggestvarious host immune strategies against the parasite [J]. Vet ImmunolImmunopathol,2003,93(3-4):81-90.
[139] MORENO M, BENAVIDEZ U, CAROL H, et al. Local and systemic immuneresponses to Echinococcus granulosus in experimentally infected dogs [J]. VetParasitol,2004,119(1):37-50.
[140] DEPLAZES P, THOMPSON R C, CONSTANTINE C C, et al. Primaryinfection of dogs with Echinococcus granulosus: systemic and local (Peyer'spatches) immune responses [J]. Vet Immunol Immunopathol,1994,40(2):171-184.
[141] KATO N, NONAKA N, OKU Y, et al. Modified cellular immune responses indogs infected with Echinococcus multilocularis [J]. Parasitol Res,2005,95(5):339-345.
[142] BARRIGA O O, AL-KHALIDI N W. Humoral immunity in the prepatentprimary infection of dogs with Echinococcus granulosus [J]. Vet ImmunolImmunopathol,1986,11(4):375-389.
[143] AL-QAOUD K M, ABDEL-HAFEZ S K. The induction of T helper type1response by cytokine gene transfection protects mice against secondaryhydatidosis [J]. Parasitol Res,2008,102(6):1151-1155.
[144] KASSIS A I, TANNER C E. Echinococcus multilocularis: complement's role invivo in hydatid disease [J]. Exp Parasitol,1977,43(2):390-395.
[145] DIAZ A, FERREIRA A M, NIETO A. Echinococcus granulosus: interactionswith host complement in secondary infection in mice [J]. Exp Parasitol,1995,80(3):473-482.
[146] FERREIRA A M, BREIJO M, SIM R B, et al. Contribution of C5-mediatedmechanisms to host defence against Echinococcus granulosus hydatid infection[J]. Parasite Immunol,2000,22(9):445-453.
[147] MEJRI N, GOTTSTEIN B. Echinococcus multilocularis metacestodemetabolites contain a cysteine protease that digests eotaxin, a CCpro-inflammatory chemokine [J]. Parasitol Res,2009,105(5):1253-1260.
[148] HERD R P, CHAPPEL R J, BIDDELL D. Immunization of dogs againstEchinococcus granulosus using worm secretory antigens [J]. Int J Parasitol,1975,5(4):395-399.
[149] FU Y, SAINT-ANDRE MARCHAL I, MARCHAL T, et al. Cellular immuneresponse of lymph nodes from dogs following the intradermal injection of arecombinant antigen corresponding to a66kDa protein of Echinococcusgranulosus [J]. Vet Immunol Immunopathol,2000,74(3-4):195-208.
[150] ZHANG W, ZHANG Z, SHI B, et al. Vaccination of dogs againstEchinococcus granulosus, the cause of cystic hydatid disease in humans [J]. JInfect Dis,2006,194(7):966-974.
[151] WU X P, FU B Q, WANG X L, et al. Identification of antigenic genes inTrichinella spiralis by immunoscreening of cDNA libraries [J]. Vet Parasitol,2009,159(3-4):272-275.
[152]CRIADO-FORNELIO A, DE ARMAS-SERRA C, GIMENEZ-PARDO C, et al.Proteolytic enzymes from Trichinella spiralis larvae [J]. Vet Parasitol,1992,45(1-2):133-140.
[153] MOCZON T, WRANICZ M. Trichinella spiralis: proteinases in the larvae [J].Parasitol Res,1999,85(1):47-58.
[154] LIU M Y, WANG X L, FU B Q, et al. Identification of stage-specificallyexpressed genes of Trichinella spiralis by suppression subtractive hybridization[J]. Parasitology,2007,134(Pt10):1443-1455.
[155] DZIK J M. Molecules released by helminth parasites involved in hostcolonization [J]. Acta Biochim Pol,2006,53(1):33-64.
[156] ROS-MORENO R M, VAZQUEZ-LOPEZ C, GIMENEZ-PARDO C, et al. Astudy of proteases throughout the life cycle of Trichinella spiralis [J]. FoliaParasitol (Praha),2000,47(1):49-54.
[157] BALASUBRAMANIAN N, TOUBARRO D, SIMOES N. Biochemical studyand in vitro insect immune suppression by a trypsin-like secreted protease fromthe nematode Steinernema carpocapsae [J]. Parasite Immunol,2010,32(3):165-175.
[158] TODOROVA V K, STOYANOV D I. Partial characterization of serineproteinases secreted by adult Trichinella spiralis [J]. Parasitol Res,2000,86(8):684-687.
[159] TODOROVA V K. Proteolytic enzymes secreted by larval stage of the parasiticnematode Trichinella spiralis [J]. Folia Parasitol (Praha),2000,47(2):141-145.
[160] ZANG X, MAIZELS R M. Serine proteinase inhibitors from nematodes and thearms race between host and pathogen [J]. Trends Biochem Sci,2001,26(3):191-197.
[161] FRANK G R, MONDESIRE R R, BRANDT K S, et al. Antibody to theDirofilaria immitis aspartyl protease inhibitor homologue is a diagnostic markerfor feline heartworm infections [J]. J Parasitol,1998,84(6):1231-1236.
[162] ROBINSON M W, MASSIE D H, CONNOLLY B. Secretion and processing ofa novel multi-domain cystatin-like protein by intracellular stages of Trichinellaspiralis [J]. Mol Biochem Parasitol,2007,151(1):9-17.
[163] MAIZELS R M, GOMEZ-ESCOBAR N, GREGORY W F, et al. Immuneevasion genes from filarial nematodes [J]. Int J Parasitol,2001,31(9):889-898.
[164] YANG Y, ZHANG Z, YANG J, et al. Oral vaccination with Ts87DNA vaccinedelivered by attenuated Salmonella typhimurium elicits a protective immuneresponse against Trichinella spiralis larval challenge [J]. Vaccine,2010,28(15):2735-2742.
[165] WEI J, GU Y, YANG J, et al. Identification and characterization of protectiveepitope of Trichinella spiralis paramyosin [J]. Vaccine,2011,29(17):3162-3168.
[166] HEIN W R, HARRISON G B. Vaccines against veterinary helminths [J]. VetParasitol,2005,132(3-4):217-222.
[167]于申业.高质量基因重组蛋白在屠宰动物旋毛虫病诊断中的应用[D].吉林：吉林大学畜牧兽医学院，2009.
[168] FENG S, WU X, WANG X, et al. Vaccination of Mice with an AntigenicSerine Protease-Like Protein Elicits a Protective Immune Response againstTrichinella Spiralis Infection [J]. J Parasitol,2012,
[169] JONES M K, GOBERT G N, ZHANG L, et al. The cytoskeleton and motorproteins of human schistosomes and their roles in surface maintenance andhost-parasite interactions [J]. Bioessays,2004,26(7):752-765.
[170] VAN HELLEMOND J J, RETRA K, BROUWERS J F, et al. Functions of thetegument of schistosomes: clues from the proteome and lipidome [J]. Int JParasitol,2006,36(6):691-699.
[171] LIGAS J A, KEREPESI L A, GALIOTO A M, et al. Specificity andmechanism of immunoglobulin M (IgM)-and IgG-dependent protectiveimmunity to larval Strongyloides stercoralis in mice [J]. Infect Immun,2003,71(12):6835-6843.
[172] KEREPESI L A, NOLAN T J, SCHAD G A, et al. Human immunoglobulin Gmediates protective immunity and identifies protective antigens against larvalStrongyloides stercoralis in mice [J]. J Infect Dis,2004,189(7):1282-1290.
[173] GALIOTO A M, HESS J A, NOLAN T J, et al. Role of eosinophils andneutrophils in innate and adaptive protective immunity to larval strongyloidesstercoralis in mice [J]. Infect Immun,2006,74(10):5730-5738.
[174] BRIGANDI R A, ROTMAN H L, YUTANAWIBOONCHAI W, et al.Strongyloides stercoralis: role of antibody and complement in immunity to thethird stage of larvae in BALB/c ByJ mice [J]. Exp Parasitol,1996,82(3):279-289.
[175] KEREPESI L A, HESS J A, NOLAN T J, et al. Complement component C3isrequired for protective innate and adaptive immunity to larval strongyloidesstercoralis in mice [J]. J Immunol,2006,176(7):4315-4322.
[176] HARRIS N, GAUSE W C. To B or not to B: B cells and the Th2-type immuneresponse to helminths [J]. Trends Immunol,2011,32(2):80-88.
[177] DIEMERT D J, BETHONY J M, HOTEZ P J. Hookworm vaccines [J]. ClinInfect Dis,2008,46(2):282-288.
[178] MCMANUS D P, LOUKAS A. Current status of vaccines for schistosomiasis[J]. Clin Microbiol Rev,2008,21(1):225-242.
[179] KOLODZIEJ-SOBOCINSKA M, DVOROZNAKOVA E, DZIEMIAN E.Trichinella spiralis: macrophage activity and antibody response in chronicmurine infection [J]. Exp Parasitol,2006,112(1):52-62.
[180] GIULIETTI A, OVERBERGH L, VALCKX D, et al. An overview of real-timequantitative PCR: applications to quantify cytokine gene expression [J].Methods,2001,25(4):386-401.
[181] ZAROS L G, BRICARELLO P A, AMARANTE A F T, et al. Quantification ofbovine. cytokine gene expression using real-time RT-PCR methodology [J].Genetics and Molecular Biology,2007,30(3):575-579.
[182] FOSTER N, ELSHEIKHA H M. The immune response to parasitic helminthsof veterinary importance and its potential manipulation for future vaccinecontrol strategies [J]. Parasitol Res,2012,110(5):1587-1599.
[183] BRUSCHI F, CHIUMIENTO L. Immunomodulation in trichinellosis: doesTrichinella really escape the host immune system?[J]. Endocr Metab ImmuneDisord Drug Targets,2012,12(1):4-15.
[184] PATEL N, KREIDER T, URBAN J F, JR., et al. Characterisation of effectormechanisms at the host:parasite interface during the immune response totissue-dwelling intestinal nematode parasites [J]. Int J Parasitol,2009,39(1):13-21.
[185] SCHOPF L R, HOFFMANN K F, CHEEVER A W, et al. IL-10is critical forhost resistance and survival during gastrointestinal helminth infection [J]. JImmunol,2002,168(5):2383-2392.
[186] LIGHTOWLERS M W, COLEBROOK A L, GAUCI C G, et al. Vaccinationagainst cestode parasites: anti-helminth vaccines that work and why [J]. VetParasitol,2003,115(2):83-123.
[187] DZIADEK B, GATKOWSKA J, BRZOSTEK A, et al. Evaluation of threerecombinant multi-antigenic vaccines composed of surface and secretoryantigens of Toxoplasma gondii in murine models of experimentaltoxoplasmosis [J]. Vaccine,2011,29(4):821-830.
[188] HALASSY B, VDOVIC V, HABJANEC L, et al. Effectiveness of novelPGM-containing incomplete Seppic adjuvants in rabbits [J]. Vaccine,2007,25(17):3475-3481.
[189] AGUADO T, ENGERS H, PANG T, et al. Novel adjuvants currently in clinicaltesting November2-4,1998, Fondation Merieux, Annecy, France: a meetingsponsored by the World Health Organization [J]. Vaccine,1999,17(19):2321-2328.
[190] HUI G S, HASHIMOTO C N. Pathways for potentiation of immunogenicityduring adjuvant-assisted immunizations with Plasmodium falciparum majormerozoite surface protein1[J]. Infect Immun,1998,66(11):5329-5336.
[191] SACHDEVA S, MOHMMED A, DASARADHI P V, et al. Immunogenicityand protective efficacy of Escherichia coli expressed Plasmodium falciparummerozoite surface protein-1(42) using human compatible adjuvants [J]. Vaccine,2006,24(12):2007-2016.
[192] GUPTA R K. Aluminum compounds as vaccine adjuvants [J]. Adv Drug DelivRev,1998,32(3):155-172.