IL-18联合SjRPS4oCB多价疫苗免疫对血吸虫病小鼠肝脏虫卵肉芽肿形成的影响
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摘要
目的观察pVAX1/IL-18联合pVAX1/SjRPS4oCB多价疫苗诱导免疫对小鼠肝脏虫卵肉芽肿形成的影响。方法 70只雌性小鼠随机分为NS组、pVAX1空质粒组、pVAX1/IL-18组、pVAX1/SjRPS4oCB组和pVAX1/SjRPS4oCB+pVAX1/IL-18组,每组小鼠注射相应质粒100μg或等量生理盐水,每隔2周加强免疫1次,共3次。末次免疫后3周,用血吸虫尾蚴以腹部贴片感染小鼠。感染后第8周剖杀小鼠,取肝组织做石蜡切片,HE染色及Masson染色后光镜下观察肝脏虫卵肉芽肿大小及虫卵周围胶原沉积情况,计算肝组织减卵率。结果与对照组相比,pVAX1/SjRPS4oCB+pVAX1/IL-18组小鼠肝脏病变程度较轻,表面虫卵结节较少,肝脏色泽、质地等接近正常肝脏,虫卵肉芽肿数量及肉芽肿面积均下降,虫卵肉芽肿周围胶原含量减少;肝减卵效果显著,减卵率为63.00%,与其它各组27.00%~52.00%比较差异均有统计学意义(P<0.05)。结论 IL-18联合pVAX1/SjRPS4oCB疫苗具有抑制抑制肝脏血吸虫虫卵肉芽肿的效果。
Objectives To examine the effect of a multivalent vaccine with pVAX1/SjRPS4 oCB and pVAX1/IL-18 on the granuloma formation caused by S.japonicumeggs in the liver of mice. Methods Seventy BABL/c mice were randomly divided into five groups:an NS control group,apVAX1 group,apVAX1/IL-18 group,apVAX1/SjRPS4 oCB vaccine group,and a pVAX1/SjRPS4 oCB+pVAX1/IL-18 group.Mice were respectively injected intramuscularly with100μg of normal saline or the plasmid 3 times every 2 weeks.Three weeks after the final injection,each mouse was infected with S.japonicumcercariae(20±1)via the abdomen.A lymphocyte proliferation experiment was used to detect the level of spleen lymphocyte proliferation in the mice.HE staining was used to detect the size of egg granulomas and Masson staining was used to determine collagen content in liver tissue.The rate of egg reduction in liver tissue was calculated. Results In the pVAX1/SjRPS4 oCB+pVAX1/IL-18 group,there were few eosinophils.Compared to the other groups,the pVAX1/SjRPS4 oCB+pVAX1/IL-18 group had a significant decrease in the average area of egg granulomas in the liver and a significant decrease in collagen content.The rate of egg reduction in liver tissue was 52% in the pVAX1/SjRPS4 oCB group and 63%in the pVAX1/SjRPS4 oCB + pVAX1/IL-18 group.The rate of egg reduction in liver tissue differed significantly in both groups(P<0.05). Conclusion IL-18 markedly reduced egg granulomas in the livers of mice immunized with an SjRPS4 oCB multivalent vaccine against S.japonicum.
Objectives To examine the effect of a multivalent vaccine with pVAX1/SjRPS4 oCB and pVAX1/IL-18 on the granuloma formation caused by S.japonicumeggs in the liver of mice. Methods Seventy BABL/c mice were randomly divided into five groups:an NS control group,apVAX1 group,apVAX1/IL-18 group,apVAX1/SjRPS4 oCB vaccine group,and a pVAX1/SjRPS4 oCB+pVAX1/IL-18 group.Mice were respectively injected intramuscularly with100μg of normal saline or the plasmid 3 times every 2 weeks.Three weeks after the final injection,each mouse was infected with S.japonicumcercariae(20±1)via the abdomen.A lymphocyte proliferation experiment was used to detect the level of spleen lymphocyte proliferation in the mice.HE staining was used to detect the size of egg granulomas and Masson staining was used to determine collagen content in liver tissue.The rate of egg reduction in liver tissue was calculated. Results In the pVAX1/SjRPS4 oCB+pVAX1/IL-18 group,there were few eosinophils.Compared to the other groups,the pVAX1/SjRPS4 oCB+pVAX1/IL-18 group had a significant decrease in the average area of egg granulomas in the liver and a significant decrease in collagen content.The rate of egg reduction in liver tissue was 52% in the pVAX1/SjRPS4 oCB group and 63%in the pVAX1/SjRPS4 oCB + pVAX1/IL-18 group.The rate of egg reduction in liver tissue differed significantly in both groups(P<0.05). Conclusion IL-18 markedly reduced egg granulomas in the livers of mice immunized with an SjRPS4 oCB multivalent vaccine against S.japonicum.
引文
[1]汪世平,陈秀春,高冬梅.我国血吸虫疫苗研究进展及应用前景[J].中国寄生虫学与寄生虫病杂志,2009,27(5):402-11.
[2]Tian Z,Wang XY,Zhou YF,et al.Schistosoma japonicum scFvIL18fusion DNA ameliorates hepatic fibrosis in schistosomiasisinfected mice via improving local concentration of IL-18in liver[J].Exp Parasitol,2013,134(4):447-54.
[3]Chen J,Pan J,Wang J,et al.Soluble egg antigens of Schistosoma japonicuminduce senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21pathway[J].Sci Rep,2016(6):30957.
[4]彭微,汪世平,郑长黎,等.日本血吸虫pVAX1/SjRPS4·CB多价疫苗免疫对小鼠肝脏虫卵肉芽肿形成的影响[J].中国人兽共患病学报,2012,28(12):1216-9.
[5]彭微,汪世平,郑长黎,等.日本血吸虫pVAX1/SjRPS4·CB多价疫苗免疫对小鼠肝脏虫卵肉芽肿形成中TNF-α表达的影响[J].中国人兽共患病学报,2013,29(6):537-42
[6]Ferrone CR,Perales MA,Goldberg SM,et al.Adjuvanticity of plasmid DNA encoding cytokines fused to immunoglobulin Fc domains[J].Clin Cancer Res,2006,12(18):5511-9.
[7]Hogg KG,Kumkate S,Mountford AP.IL-10regulates early IL-12-mediated immune responses induced by the radiation-attenuated schistosome vaccine[J].Int Immunol,2003,15(12):1451-9.
[8]Hogg KG,Kumkate S,Anderson S,et al.Interleukin-12p40secretion by cutaneous CD11c+and F4/80+cells is a major feature of the innate immune response in mice that develop Th1-mediated protective immunity to Schistosoma mansoni[J].Infect Immun,2003,71(6):3563-71.
[9]张立煌,姚航平.吡喹酮联合IL-18基因治疗血吸虫感染小鼠对免疫功能的影响[J].中华微生物与免疫学杂志,2001,21(1):87-90.
[10]Shi XJ,Wang B,Wang M,et al.Immune enhancing effects of recombinant bovine IL-18on foot-and-mouth disease vaccination in mice model[J].Vaccine,2007,25(7):1257-64.
[11]Siva Reddy K,Muralidhar Rao D,Badrinaryana N,et al.Enhancement of DNA vaccine(P12A3C-pcDNA)efficacy against foot-and-mouth disease by coadministration of interleukin-18-expressing(IL18pcDNA)plasmid in guinea-pigs[J].Immunol Med Microbiol,2010,60(3):261-9.
[12]Eberl M,Beck E,Coulson PS,et al.IL-18potentiates the adjuvant properties of IL-12in the induction of a strong Th1type immune response against a recombinant antigen[J].Vaccine,2000,18(19):2002-8.
[13]葛宇曦,张键锋,潘永明,等.颈动脉注射血吸虫虫卵建立兔脑肉芽肿模型的研究[J].中国病原生物学杂志,2017,12(9):864-7,878.
[14]袁发浒,冯金梅,刘锴,等.EGCG对日本血吸虫感染小鼠TIMP-1及α-SMA表达和肝纤维化的影响[J].中国病原生物学杂志,2016,11(5):428-33.
[15]Dupre L,Kremer L,Wolowczuk I,et al.Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection[J].Vaccine,2001,19(11-12):1373-80.
[16]Wei F,Liu Q,Gao S,et al.Enhancement by IL-18of the protective effect of a Schistosoma japonicum 26kDa GST plasmid DNA vaccine in mice[J].Vaccine,2008,26(33):4145-9.
[17]Wei F,Liu Q,Zhai Y,et al.IL-18enhances protective effect in mice immunized with a Schistosoma japonicum FABP DNA vaccine[J].Acta Trop,2009,111(3):284-8.
[18]门静涛,刘全,商利民,等.IL-18增强日本血吸虫DNA疫苗Sj23的免疫保护效果[J].中国兽医学报,2009,29(5):610-4.
[2]Tian Z,Wang XY,Zhou YF,et al.Schistosoma japonicum scFvIL18fusion DNA ameliorates hepatic fibrosis in schistosomiasisinfected mice via improving local concentration of IL-18in liver[J].Exp Parasitol,2013,134(4):447-54.
[3]Chen J,Pan J,Wang J,et al.Soluble egg antigens of Schistosoma japonicuminduce senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21pathway[J].Sci Rep,2016(6):30957.
[4]彭微,汪世平,郑长黎,等.日本血吸虫pVAX1/SjRPS4·CB多价疫苗免疫对小鼠肝脏虫卵肉芽肿形成的影响[J].中国人兽共患病学报,2012,28(12):1216-9.
[5]彭微,汪世平,郑长黎,等.日本血吸虫pVAX1/SjRPS4·CB多价疫苗免疫对小鼠肝脏虫卵肉芽肿形成中TNF-α表达的影响[J].中国人兽共患病学报,2013,29(6):537-42
[6]Ferrone CR,Perales MA,Goldberg SM,et al.Adjuvanticity of plasmid DNA encoding cytokines fused to immunoglobulin Fc domains[J].Clin Cancer Res,2006,12(18):5511-9.
[7]Hogg KG,Kumkate S,Mountford AP.IL-10regulates early IL-12-mediated immune responses induced by the radiation-attenuated schistosome vaccine[J].Int Immunol,2003,15(12):1451-9.
[8]Hogg KG,Kumkate S,Anderson S,et al.Interleukin-12p40secretion by cutaneous CD11c+and F4/80+cells is a major feature of the innate immune response in mice that develop Th1-mediated protective immunity to Schistosoma mansoni[J].Infect Immun,2003,71(6):3563-71.
[9]张立煌,姚航平.吡喹酮联合IL-18基因治疗血吸虫感染小鼠对免疫功能的影响[J].中华微生物与免疫学杂志,2001,21(1):87-90.
[10]Shi XJ,Wang B,Wang M,et al.Immune enhancing effects of recombinant bovine IL-18on foot-and-mouth disease vaccination in mice model[J].Vaccine,2007,25(7):1257-64.
[11]Siva Reddy K,Muralidhar Rao D,Badrinaryana N,et al.Enhancement of DNA vaccine(P12A3C-pcDNA)efficacy against foot-and-mouth disease by coadministration of interleukin-18-expressing(IL18pcDNA)plasmid in guinea-pigs[J].Immunol Med Microbiol,2010,60(3):261-9.
[12]Eberl M,Beck E,Coulson PS,et al.IL-18potentiates the adjuvant properties of IL-12in the induction of a strong Th1type immune response against a recombinant antigen[J].Vaccine,2000,18(19):2002-8.
[13]葛宇曦,张键锋,潘永明,等.颈动脉注射血吸虫虫卵建立兔脑肉芽肿模型的研究[J].中国病原生物学杂志,2017,12(9):864-7,878.
[14]袁发浒,冯金梅,刘锴,等.EGCG对日本血吸虫感染小鼠TIMP-1及α-SMA表达和肝纤维化的影响[J].中国病原生物学杂志,2016,11(5):428-33.
[15]Dupre L,Kremer L,Wolowczuk I,et al.Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection[J].Vaccine,2001,19(11-12):1373-80.
[16]Wei F,Liu Q,Gao S,et al.Enhancement by IL-18of the protective effect of a Schistosoma japonicum 26kDa GST plasmid DNA vaccine in mice[J].Vaccine,2008,26(33):4145-9.
[17]Wei F,Liu Q,Zhai Y,et al.IL-18enhances protective effect in mice immunized with a Schistosoma japonicum FABP DNA vaccine[J].Acta Trop,2009,111(3):284-8.
[18]门静涛,刘全,商利民,等.IL-18增强日本血吸虫DNA疫苗Sj23的免疫保护效果[J].中国兽医学报,2009,29(5):610-4.