牛结核流行病学和树突状细胞感染毒力M.bovis的基因表达
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摘要
牛结核病是由分枝杆菌引起的包括人和家畜以及野生动物发病的一种慢性消耗性人兽共患传染病,被国际动物卫生组织(OIE)定为B类动物传染病。奶牛结核病,与布鲁氏菌病并称奶牛的“两病”,历史是严重威胁奶业健康发展的重大传染病。目前全球有约5000万头以上的牛感染了牛结核,每年造成大约30亿美元的经济损失。另据有关资料报道,世界上结核病人中约有15%是通过饮用了结核病牛的奶而生病的。因此,早在1960年世界卫生组织专家委员会第七次会议中便指出:“在那些还存在牛结核病问题的国家中,人类始终受到它的威胁,除非扑灭牛结核病,否则人类结核病的控制是不会成功的”。有数据显示,解放初期,我国奶牛结核阳性率高达80%。随着近年来我国奶业的迅速发展,牛结核病的对奶业健康发展具有越来越严重的威胁,奶牛结核病的防控也愈来愈受到重视。但是我国牛结核病的流行状况却十分不清楚,背景不明使我国对牛结核病的防控遇到的最大障碍之一。另外,牛结核病因缺乏疫苗而无法对易感牛群进行免疫预防,了解结核病的免疫特点是开发新是开发新疫苗、新药物来防治结核病的基础性工作。树突状细胞是体内专职的免疫提呈细胞。因此,本研究从牛结核病的分子流行病学和牛分枝杆菌与树突状细胞的相互作用等角度进行了初步探讨,主要获得以下结果:
1.奶牛牛结核病血清学调查
严格按照分层随机采样方法,从全国30个省、市、自治区采集到1344份奶牛血清,使用牛结核病特异性抗体ELISA检测试剂盒检测牛结核病,结果发现22份阳性血清,总体阳性率为1.6%。30个省中有19个省未检出阳性血清,有11个省发现有阳性结果,各省份的阳性率从1.1%至20%不等。另外对某省进行16个奶牛场进行高密度采集,对782份血清进行ELISA检测,结果共检测出59份阳性血清,总体阳性率为7.54%。16个牛场中,有3个奶牛场未检出阳性,其余13家奶牛场均有阳性结果。牛场间阳性率从0.87-41.18%不等,说明牛结核病在牛场间呈散在分布。
2.分枝杆菌分子流行病学研究
采集结核病抗体阳性奶牛的鼻腔分泌物进行分枝杆菌培养,结果共培养出17个阳性培养物。使用生化方法和PCR鉴定,17株阳性培养物,有1株为非结核分枝杆菌,3株牛分枝杆菌和13株结核分枝杆菌。使用Spoligotyping和MIRU分子分型方法,发现13株结核分枝杆菌基因型为北京基因型,MIRU pattern为2223-2517-3533。同时对当地结核病防治院所的105株结核分枝杆菌临床分离株进行的分子分型未发现人中有牛分枝杆菌感染,且MIRU pattern为2223-2517-3533的北京基因型菌株为人中感染的主要菌株之一,说明奶牛感染的结核分枝杆菌与人结核病之间具有分子流行病学联系。
3.牛分枝杆菌与小鼠树突状细胞相互作用研究
分别用毒力牛分枝杆菌和卡介苗感染小鼠未成熟树突状细胞,感染比(MOI)为10,感染后16小时采用小鼠全基因组表达谱芯片检测感染的树突状细胞差异基因的表达。结果共发现差异基因36个,基中上调基因27个,主要包括ptgs2、ptges等前列腺素合成酶基因、il-1、i1-12、tnf等细胞因子基因和ccl4、cxcl1等趋化因子基因;下调基因9个,主要包括dffa、ccr2和cnr2等。利用实时定量RT-PCR证实进一步证实基因芯片的检测结果,发现ptgs2、il-12a、cxcl1、tnf,dffa等基因的差异表达结果与芯片结果基本相符。用ELISA检测试剂盒检测感染树突状细胞分泌的细胞因子水平的变化,发现感染毒力牛分枝杆菌的树突状细胞分泌IL-12和IL-1β细胞因子的量分别是感染无毒卡介苗的树突状细胞的1.6倍和1.9倍,t检验表明两组数据间差异显著。以上结果表明,和感染卡介苗相比,感染牛分枝杆菌毒力株能促进树突状细胞合成大量前列腺素、细胞因子和趋化因子,同时下调另一些相关基因。这些基因表达谱的差异可能通过调控机体免疫系统功能,使毒力牛分枝杆菌得以在体内存活、散播、并激活特定的免疫反应。
Bovine tuberculosis is a chronic consumptive zoonosis casued by Mycoabcterium tuberculosis complex,and is considered as B type infectious disease by OIE.Bovine tuberculosis is referred as one of List 2 disease of cows,causing great economic loss in cow industry and a continuing threat to public health.Currently,more than 50 million cattle were affected by bovine tuberculosis,and caused 3 billion US dollars of economic loss annually.It is reported that 15%tuberculosis cases in the world due to drinking milk from sick cows.Therefore,the experts in World Health Organization(WHO) committee said that tuberculosis can not be controlled unless bovine tuberculosis is eradicated.In 1950s,the positive rate of bovine tuberculosis is up to 80%in China.Along with the rapid development of dairy industry,bovine tuberculosis is becoming more and more a serious threat to Chinese dairy industry and public health.Thus,control of bovine tuberculosis attracts much more attention nowadays.However,lack of the epidemic data and effective vaccine of bovine tuberculosis posed the greatest obstacle to control bovine tuberculosis in China.Furthermore,the knowledge of immunity to tuberculosis is essential to develop new vaccines and drugs to eradicate tuberculosis.Dendritic cells are potent professional antigen presenting cells.Therefore,this work was aimed to investigate the molecular epidemiology of bovine tuberculosis and the interaction between Mycobacterium bovis and dendritic cells.The main results were summarized as follows:
1.National serological survey of bovine tuberculosis
1344 bovine sera from national serum bank representing 30 provinces of China were used to make serological epidemiological investigation.The sera were collected by stratified random sampling and subjected to antibody detection to specific antigens MPB70/MPB83/Esat-6/CFP 10 of M.bovis.As a result,22 sera were found to be positive, and the overall positive rate was 1.6%.19 of 30 provinces did not possess positive sera, but 11 did.The positive rates ranged from 1.1%to 20%among provinces.Moreover,782 dairy cow sera from 16 local cow herds were collected,and subjected to antibody test with ELISA.59 sera were found to be positive,and the overall positive rate is 7.54%.13 of 16 herds were found positive samples,and the positive rate ranged from 0.87%to 41.18%.
2.Mycobacterial molecular epidemiology investigation
Nasal swab collected from antibody positive cows were subjected to culture,and 17 isolates were obtained.By using biochemical and PCR identification,1 of 17 isolates was non-tuberculous mycobacterium,3 were M.bovis and 13 were M.tuberculosis. Furthermore,13 M.tb isolates were identified to be Beijing genotype by spoligotyping and share a 2223-2517-3533 MIRU pattern.Meanwhile,the investigation of clinical isolates from local human TB patients revealed there is no M.bovis in 105 clinical isolates.Nevertheless,the same genotype(2223-2517-3533,Beijing genotype) were found to be a main cluster of human infection,which there was an molecular epidemiological link between bovine and human tuberculosis.
3.The interaction between murine dendritic cells and Mycobacterium bovis
Murine bone marrow derived immature dendritic cells were respectively infected by virulent Mycobacterium bovis and avirulent Mycobacterium bovis BCG.at an MOI of 10. The total RNA of dendritic cells was extracted at 16h post-infection,and subjected to murine whole genome microarray to screen the gene transcription difference.36 transcripts were found to have different transcription amount.Among them,27 transcripts were up-regulated in virulent M.bovis infected dendritic cells,including genes coding prostaglandin synthesis enzyme(ptgs2,ptges),cytokines(il-1,il-12,tnf) and chemokines (ccl4,cxcl1),while other 9 transcripts were down-regulated in virulent M.bovis infected dendritic cells,including dffa,ccr2,cnr2 and so on.By verification using Realtime PCR, the up- or down-regulated of ptgs2,il-12a,cxcl1,tnf and dffa were found to be consistent with microarray detection.The protein level changes of IL-12 and IL-1βwere also tested with commercial ELISA kits.Virulent M.bovis infected dendritic cells secreted 1.6-fold and 1.9-fold more IL-12 and IL-1βthan those of avirulent M.bovis BCG infected dendritic cells.These data suggest that murine dendritic cells infected by virulent M. bovis manipulate immune system and help virulent M.bovis survive,spread and activate immune system by increasing synthesis of prostaglandin,cytokines and chemokines and decrease some other genes.
1.奶牛牛结核病血清学调查
严格按照分层随机采样方法,从全国30个省、市、自治区采集到1344份奶牛血清,使用牛结核病特异性抗体ELISA检测试剂盒检测牛结核病,结果发现22份阳性血清,总体阳性率为1.6%。30个省中有19个省未检出阳性血清,有11个省发现有阳性结果,各省份的阳性率从1.1%至20%不等。另外对某省进行16个奶牛场进行高密度采集,对782份血清进行ELISA检测,结果共检测出59份阳性血清,总体阳性率为7.54%。16个牛场中,有3个奶牛场未检出阳性,其余13家奶牛场均有阳性结果。牛场间阳性率从0.87-41.18%不等,说明牛结核病在牛场间呈散在分布。
2.分枝杆菌分子流行病学研究
采集结核病抗体阳性奶牛的鼻腔分泌物进行分枝杆菌培养,结果共培养出17个阳性培养物。使用生化方法和PCR鉴定,17株阳性培养物,有1株为非结核分枝杆菌,3株牛分枝杆菌和13株结核分枝杆菌。使用Spoligotyping和MIRU分子分型方法,发现13株结核分枝杆菌基因型为北京基因型,MIRU pattern为2223-2517-3533。同时对当地结核病防治院所的105株结核分枝杆菌临床分离株进行的分子分型未发现人中有牛分枝杆菌感染,且MIRU pattern为2223-2517-3533的北京基因型菌株为人中感染的主要菌株之一,说明奶牛感染的结核分枝杆菌与人结核病之间具有分子流行病学联系。
3.牛分枝杆菌与小鼠树突状细胞相互作用研究
分别用毒力牛分枝杆菌和卡介苗感染小鼠未成熟树突状细胞,感染比(MOI)为10,感染后16小时采用小鼠全基因组表达谱芯片检测感染的树突状细胞差异基因的表达。结果共发现差异基因36个,基中上调基因27个,主要包括ptgs2、ptges等前列腺素合成酶基因、il-1、i1-12、tnf等细胞因子基因和ccl4、cxcl1等趋化因子基因;下调基因9个,主要包括dffa、ccr2和cnr2等。利用实时定量RT-PCR证实进一步证实基因芯片的检测结果,发现ptgs2、il-12a、cxcl1、tnf,dffa等基因的差异表达结果与芯片结果基本相符。用ELISA检测试剂盒检测感染树突状细胞分泌的细胞因子水平的变化,发现感染毒力牛分枝杆菌的树突状细胞分泌IL-12和IL-1β细胞因子的量分别是感染无毒卡介苗的树突状细胞的1.6倍和1.9倍,t检验表明两组数据间差异显著。以上结果表明,和感染卡介苗相比,感染牛分枝杆菌毒力株能促进树突状细胞合成大量前列腺素、细胞因子和趋化因子,同时下调另一些相关基因。这些基因表达谱的差异可能通过调控机体免疫系统功能,使毒力牛分枝杆菌得以在体内存活、散播、并激活特定的免疫反应。
Bovine tuberculosis is a chronic consumptive zoonosis casued by Mycoabcterium tuberculosis complex,and is considered as B type infectious disease by OIE.Bovine tuberculosis is referred as one of List 2 disease of cows,causing great economic loss in cow industry and a continuing threat to public health.Currently,more than 50 million cattle were affected by bovine tuberculosis,and caused 3 billion US dollars of economic loss annually.It is reported that 15%tuberculosis cases in the world due to drinking milk from sick cows.Therefore,the experts in World Health Organization(WHO) committee said that tuberculosis can not be controlled unless bovine tuberculosis is eradicated.In 1950s,the positive rate of bovine tuberculosis is up to 80%in China.Along with the rapid development of dairy industry,bovine tuberculosis is becoming more and more a serious threat to Chinese dairy industry and public health.Thus,control of bovine tuberculosis attracts much more attention nowadays.However,lack of the epidemic data and effective vaccine of bovine tuberculosis posed the greatest obstacle to control bovine tuberculosis in China.Furthermore,the knowledge of immunity to tuberculosis is essential to develop new vaccines and drugs to eradicate tuberculosis.Dendritic cells are potent professional antigen presenting cells.Therefore,this work was aimed to investigate the molecular epidemiology of bovine tuberculosis and the interaction between Mycobacterium bovis and dendritic cells.The main results were summarized as follows:
1.National serological survey of bovine tuberculosis
1344 bovine sera from national serum bank representing 30 provinces of China were used to make serological epidemiological investigation.The sera were collected by stratified random sampling and subjected to antibody detection to specific antigens MPB70/MPB83/Esat-6/CFP 10 of M.bovis.As a result,22 sera were found to be positive, and the overall positive rate was 1.6%.19 of 30 provinces did not possess positive sera, but 11 did.The positive rates ranged from 1.1%to 20%among provinces.Moreover,782 dairy cow sera from 16 local cow herds were collected,and subjected to antibody test with ELISA.59 sera were found to be positive,and the overall positive rate is 7.54%.13 of 16 herds were found positive samples,and the positive rate ranged from 0.87%to 41.18%.
2.Mycobacterial molecular epidemiology investigation
Nasal swab collected from antibody positive cows were subjected to culture,and 17 isolates were obtained.By using biochemical and PCR identification,1 of 17 isolates was non-tuberculous mycobacterium,3 were M.bovis and 13 were M.tuberculosis. Furthermore,13 M.tb isolates were identified to be Beijing genotype by spoligotyping and share a 2223-2517-3533 MIRU pattern.Meanwhile,the investigation of clinical isolates from local human TB patients revealed there is no M.bovis in 105 clinical isolates.Nevertheless,the same genotype(2223-2517-3533,Beijing genotype) were found to be a main cluster of human infection,which there was an molecular epidemiological link between bovine and human tuberculosis.
3.The interaction between murine dendritic cells and Mycobacterium bovis
Murine bone marrow derived immature dendritic cells were respectively infected by virulent Mycobacterium bovis and avirulent Mycobacterium bovis BCG.at an MOI of 10. The total RNA of dendritic cells was extracted at 16h post-infection,and subjected to murine whole genome microarray to screen the gene transcription difference.36 transcripts were found to have different transcription amount.Among them,27 transcripts were up-regulated in virulent M.bovis infected dendritic cells,including genes coding prostaglandin synthesis enzyme(ptgs2,ptges),cytokines(il-1,il-12,tnf) and chemokines (ccl4,cxcl1),while other 9 transcripts were down-regulated in virulent M.bovis infected dendritic cells,including dffa,ccr2,cnr2 and so on.By verification using Realtime PCR, the up- or down-regulated of ptgs2,il-12a,cxcl1,tnf and dffa were found to be consistent with microarray detection.The protein level changes of IL-12 and IL-1βwere also tested with commercial ELISA kits.Virulent M.bovis infected dendritic cells secreted 1.6-fold and 1.9-fold more IL-12 and IL-1βthan those of avirulent M.bovis BCG infected dendritic cells.These data suggest that murine dendritic cells infected by virulent M. bovis manipulate immune system and help virulent M.bovis survive,spread and activate immune system by increasing synthesis of prostaglandin,cytokines and chemokines and decrease some other genes.
引文
1.白璧,肖康,金志强.贵阳市乌当区奶牛结核病检疫情况.中国兽医杂志,2003,39(2):46
2.蔡宝祥.家畜传染病学第四版.北京:中国农业出版社,2001.
3.陈敬,董德琼,杨渝浩.白介素-12与结核病.国外医学呼吸系统分册,2002,22(4):220-222
4.傅义娟,傅国璋,王生祥.青海省奶牛结核病的调查与防制.中国兽医杂志,2004,40(6):31
5.富立国,王文,赵艳春.奶牛布鲁氏杆菌病、结核病检疫监测的综合措施.黑龙江畜牧兽医,2004,5:77
6.甘海霞,何宝祥,刘棋.牛结核病的危害与流行情况.广西畜牧兽医,2007,23(6):286-288
7.高爱萍,韩方伟,戚磊,段素华.江苏徐州地区奶牛布病、结核病的监测结果与分析.畜牧与兽医,2004,36(5):31-32
8.高建新,谢雪山,陈家军,郑建云,马翔,李忠孝.巍山县奶牛布氏杆菌病、结核病检测的思考.云南畜牧兽医,2005,1:34
9.何邵阳.牛结核病研究进展.预防兽医学研究进展,2001,3(4):34-39
10.黄纪铨.牛结核病.福建畜牧兽医,2000,22(6):39-46
11.黄锦江.广州地区奶牛结核病、布氏病的检疫与防制.广东畜牧兽医科技,1997,22(3):27-28
12.黄瑛,于三科,王建军.新疆昌吉市奶牛结核病、布鲁菌病的检测.动物医学进展,2005,26(10):116-117
13.姬学谦.临夏州奶牛结核病的临测与防制.甘肃畜牧兽医,2004,34(4):18-19
14.吉生宏,祁永秀.西宁市奶牛“两病”监测检疫.畜牧兽医杂志,2005,24(2):34-35
15.季旭仁,金大春,王跃川.瑞安市奶牛结核病监测现状及应对措施.浙江畜牧兽医,2004,2(30
16.孔令萍,罗成波,李建元.兴义市奶牛结核病的调查.贵州畜牧兽医,2003,27(1):11
17.李川,谭亚娣,陈颖钰,胡巧云,马艳,张桂荣,钦博,晁彦杰,陈焕春,郭爱珍.牛IFN-γ原核表达、单克隆抗体制备及其ELISA检测方法的建立.生物工程学报,2007,23(01):40-45
18.李舵,盛卓君,刘进,彭小玲,乔红伟,陈德坤.新疆部分地区牛结核病PPD 监测与分析.动物医学进展,2006,27(4):99-101
19.李积善,许英芬,逮克庆,彭生,晁学元,秦振华,谷玉辉.奶牛结核检测报告.青海畜牧兽医杂志,2003,33(1):46
20.李建玲,陈彪,张婕,王文秀,郭亚军.乌鲁木齐地区奶牛结核病、布鲁氏菌病检疫现状分析与措施.中国食草动物,2005,25(1):37-38
21.李连波,齐梅.牡丹江市奶牛结核病的检疫报告.中国动物检疫,2001,18(6):28-29
22.李晓梅,贺亚雄,沙勇波,韦志芳.一起奶牛结核病的处理与反思.中国兽医杂志,2004,40(3):58-59
23.李业福.奶牛结核病的临测报告.中国兽药杂志,2004,38(6):48-49
24.刘道新,谈志祥,邱立新,鲁杏华,王昌建.湖南省动物布鲁氏菌病和奶牛结核病的调查.湖南畜牧兽医,2003,4:27-28
25.刘思国,王春来,张秀华,郭设平,郭洋,邵美丽.牛结核病病原生态学和流行病学研究.中国畜牧兽医,2005,32(3):60-62
26.刘思国,于辉,宫强.牛结核病研究进展.畜牧兽医科技信息,2003,19(10):10-14
27.陆立权,宋启文,熊毅,磨龙春,郭建刚,何贻坚.广西奶牛结核病和布鲁氏菌病的调查.广西农业科学,1998,2:83-85
28.母安雄,陆永干,应小飞,谷根林,杨宗照,陶益.杭州市奶牛结核病和布氏杆菌病检测结果.浙江畜牧兽医,2003,3:28-29
29.钦博,万学济,胡巧云,喻正军,晁彦杰,郭爱珍,陈焕春,谭亚娣.牛型分枝杆菌MPB70蛋白胶乳凝集方法的建立及应用.中国预防兽医学报.2007,29(01):58-62
30.秦鹏,胡厚如.2005年金安区奶牛结核病的监测结果分析.现代农业科技,2006,5:67
31.全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调 查报告.中华结核和呼吸杂志,2002,25(01):3-7
32.任岩.兰州市西固区奶牛结核病感染调查.中国动物检疫,2003,12:35
33.沈文,张再清,焦忠新,周林,张登海.石河子地区某奶牛场结核病的检疫调查.青海畜牧兽医杂志,2006,36(5):23-24
34.史明基,王建中,刘果,蔡斌.兴化市奶牛结核病的检疫.中国动物检疫,2006,23(2):31-32
35.陶昆,卢贤瑜.肿瘤坏死因子alpha抗结核免疫作用研究进展.国际检验医学杂志,2006,27(2):143-145
36.王明茂,胡祖榕,王孟华,张洪光,蔡传生,吴秀珠.对散养乳牛结核病的普查.福建畜牧兽医,1997,2:33
37.王永康,叶元亨.上海奶牛结核病和布氏杆菌病的控制.乳业科学与技术,2004,3:133-135
38.卫生部.2008年1月全国法定报告传染病疫情.2008.http://www.moh.gov.cn/newshtml/21160.htm
39.吴波,张书环,邓铨涛,项杰,陈军,刘朝,陈鑫,宋念华,陶淑珍,黄继根,韩永佩,赵波,林祥梅,陈焕春,郭爱珍.四种牛分枝杆菌特异性蛋白融合表达及在牛结核病诊断中的临床应用.中国人兽共患病杂志,2007,23(9):41-44
40.吴磊,万庆铭,苏翠萍,杨红.奶牛结核病的普查.四川畜牧兽医,2003,30(3):47
41.吴志仓.永靖县奶牛结核病检疫情况及病原鉴别试验.甘肃畜牧兽医,2001,31(1):10-11
42.吴志明,刘莲芝,李桂喜.动物疫病防治知识.北京:中国农业出版社,2006.
43.肖和平.结核病流行的近期特点.中国临床医生,2004,32(7):2-4
44.肖凌,魏雅稚,夏飞,刘胜武.结核杆菌Hsp65与EGFP融合基因的构建及DC 疫苗的制备.细胞与分子免疫学杂志.2005,21(1):13-16
45.新德,安宁.新疆博乐奶牛结核病调查.新疆畜牧业,2007,1:38-39
46.徐庆,汤碧娥,张志琴.环氧化酶-2的研究进展.中国误诊学杂志,2006,6(19):2705-3707
47.杨家和,钱其军,吴孟超,郭亚军.白介素12:重要的免疫调节因子.世界华人消化杂志,1999,7(1):71-72
48.杨卫冲,焦新安.牛结核病诊断技术研究进展.中国人畜共患病杂志,2004,20(12):1090-1093
49.裔群英,卞红春.盐城地区奶牛结核病和布鲁氏菌病检测及分析.中国动物检疫,2005,22(11):27
50.尹徐凤,李香云,传为军.庆阳县奶牛结核病临测报告.甘肃农村科技,2002,4:18-19
51.应如朗,余全法,鲍伟华,王敏亚,王维金.关于宁波市奶牛结核病的检测报告.浙江畜牧兽医,2001,2:28
52.张桂荣,万学济,陈颖钰,吴波,晁彦杰,吕文,钦博,郭爱珍,陈焕春,谭亚娣.间接ELISA检测牛分枝杆菌抗体方法的建立及初步应用.中国预防兽医学报.2007,29(29):555-560
53.张书环,吴波,曹莎,陈颖钰,晁彦杰,陈焕春,郭爱珍.牛分枝杆菌抗原MPB70、MPB83、CFP-10和ESAT-6的融合表达及相关特性分析.中国人兽共患病学报.2007,23(12):1238-1242
54.张书环,杨俊兴,晁彦杰,颜邦芬,吴波,曹莎,陈颖钰,谭亚娣,陈焕春,郭爱珍.牛结核病抗体胶体金快速检测技术的建立和应用.动物医学进展.2007,28(07):17-24
55.张铁源,康桂花,李华,金正男.前列腺素与非甾体抗炎免疫药.延边医学院学报,1994,17(1):58-61
56.赵国财,祁尚绥,刘学森,宋维军.东营区奶牛结核病检疫报告.中国动物检疫,2001,18(4):37
57.朱长光,李志军,李宏伟.北京市某奶牛场检出结核、副结核阳性牛.中国动物检疫,1999,16(4):19-20
58.Alaniz R C,Sandall S,Thomas E K,Wilson C B.Increased dendritic cell numbers impair protective immunity to intracellular bacteria despite augmenting antigen-specific CD8+ T lymphocyte responses.J Immunol,2004,172(6):3725-3735
59.Aranaz A,Liebana E,Mateos A,Dominguez L,Vidal D,Domingo M,Gonzolez O,Rodriguez-Ferri E F,Bunschoten A E,Van Embden J D,Cousins D.Spacer oligonucleotide typing of Mycobacterium bovis strains from cattle and other animals:a tool for studying epidemiology of tuberculosis.Journal of Clinical Microbiology, 1996,34(11):2734-2740
60. Bafica A, Scanga C A, Feng C G, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. The Journal of Experimental Medicine, 2005, 202(12):1715-1724
61. Bean A G, Roach D R, Briscoe H, France M P, Korner H, Sedgwick J D, Britton W J. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J Immunol, 1999,162(6):3504-3511
62. Behr M A, Wilson M A, Gill W P, Salamon H, Schoolnik G K, Rane S, Small P M. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science, 1999,284(5419): 1520-1523
63. Bodnar K A, Serbina N V, Flynn J L. Fate of Mycobacterium tuberculosis within murine dendritic cells. Infection and Immunity, 2001,69(2):800-809
64. Brosch R, Gordon S V, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald J K, Golby P, Garcia J N, Hewinson R G, Behr M A, Quail M A, Churcher C, Barrell B G, Parkhill J, Cole S T. Genome plasticity of BCG and impact on vaccine efficacy. Proceedings of the National Academy of Sciences of the United States of America, 2007,104(13):5596-5601
65. Brustmann H. DNA fragmentation factor (DFF45): expression and prognostic value in serous ovarian cancer. Pathology, Research and Practice, 2006,202(10):713-720
66. Camus J C, Pryor M J, Medigue C, Cole S T. Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology, 2002,148(Pt 10):2967-2973
67. Cole S T, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon S V, Eiglmeier K, Gas S, Barry C E, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 1998, 393(6685):537-544
68. Cole S T, Eiglmeier K, Parkhill J, James K D, Thomson N R, Wheeler P R, Honore N, Gamier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies R M, Devlin K, Duthoy S, Feltwell T, Fraser A, et al. Massive gene decay in the leprosy bacillus. Nature, 2001,409(6823): 1007-1011
69. Cosivi O, Grange J M, Daborn C J, Raviglione M C, Fujikura T, Cousins D, Robinson R A, Huchzermeyer H F A K, de Kantor I, Meslin F X. Zoonotic Tuberculosis due to Mycobacterium bovis in Developig Countries. Emerging Infectious Diseases. 1998,4(1):59-70
70. Cousins D V, Skuce R A, Kazwala R R, van Embden J D. Towards a standardized approach to DNA fingerprinting of Mycobacterium bovis. International Union Against Tuberculosis and Lung Disease, Tuberculosis in Animals Subsection. Int J Tuberc Lung Dis, 1998,2(6):471-478
71. Cousins D V, Williams S N, Dawson D J. Tuberculosis due to Mycobacterium bovis in the Australian population: DNA typing of isolates, 1970-1994. Int J Tuberc Lung Dis, 1999, 3(8):722-731
72. Cowan L S, Mosher L, Diem L, Massey J P, Crawford J T. Variable-number tandem repeat typing of Mycobacterium tuberculosis isolates with low copy numbers of IS6110 by using mycobacterial interspersed repetitive units. Journal of Clinical Microbiology, 2002,40(5): 1592-1602
73. Demangel C, Bean A G, Martin E, Feng C G, Kamath A T, Britton W J. Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells. European Journal of Immunology, 1999,29(6): 1972-1979
74. Dulphy N, Herrmann J L, Nigou J, Rea D, Boissel N, Puzo G, Charron D, Lagrange P H, Toubert A. Intermediate maturation of Mycobacterium tuberculosis LAM-activated human dendritic cells. Cellular Microbiology, 2007, 9(6): 1412-1425
75. Fleischmann R D, Alland D, Eisen J A, Carpenter L, White O, Peterson J, DeBoy R, Dodson R, Gwinn M, Haft D, Hickey E, Kolonay J F, Nelson W C, Umayam L A, Ermolaeva M, Salzberg S L, Delcher A, Utterback T, Weidman J, Khouri H, et al. Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. Journal of Bacteriology, 2002,184(19):5479-5490
76. Fricke I, Mitchell D, Mirtelstadt J, Lehan N, Heine H, Goldmann T, Bohle A, Brandau S. Mycobacteria induce IFN-gamma production in human dendritic cells via triggering of TLR2. J Immunol, 2006,176(9):5173-5182
77. Frothingham R, Meeker-O'Connell W A. Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology, 1998,144 (Pt 5): 1189-1196
78. Gamier T, Eiglmeier K, Camus J C, Medina N, Mansoor H, Pryor M, Duthoy S, Grondin S, Lacroix C, Monsempe C, Simon S, Harris B, Atkin R, Doggett J, Mayes R, Keating L, Wheeler P R, Parkhill J, Barrell B G, Cole S T, et al. The complete genome sequence of Mycobacterium bovis. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(13):7877-7882
79. Geijtenbeek T B, Van Vliet S J, Koppel E A, Sanchez-Hernandez M, Vandenbroucke-Grauls C M, Appelmelk B, Van Kooyk Y. Mycobacteria target DC-SIGN to suppress dendritic cell function. The Journal of Experimental Medicine, 2003,197(1):7-17
80. Giacomini E, Sotolongo A, Iona E, Severa M, Remoli M E, Gafa V, Lande R, Fattorini L, Smith I, Manganelli R, Coccia E M. Infection of human dendritic cells with a Mycobacterium tuberculosis sigE mutant stimulates production of high levels of interleukin-10 but low levels of CXCL10: impact on the T-cell response. Infection and Immunity, 2006, 74(6):3296-3304
81. Haddad N, Masselot M, Durand B. Molecular differentiation of Mycobacterium bovis isolates. Review of main techniques and applications. Research in Veterinary Science, 2004, 76(1): 1-18
82. Hanekom W A, Mendillo M, Manca C, Haslett P A, Siddiqui M R, Barry C, Kaplan G. Mycobacterium tuberculosis inhibits maturation of human monocyte-derived dendritic cells in vitro. The Journal of Infectious Diseases, 2003,188(2):257-266
83. Henderson R A, Watkins S C, Flynn J L. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J Immunol, 1997, 159(2):635-643
84. Huang Q, Liu D, Majewski P, Schulte L C, Korn J M, Young R A, Lander E S, Hacohen N. The plasticity of dendritic cell responses to pathogens and their components. Science, 2001,294(5543):870-875
85. Huard R C, Lazzarini L C, Butler W R, van Soolingen D, Ho J L. PCR-based method to differentiate the subspecies of the Mycobacterium tuberculosis complex on the basis of genomic deletions. Journal of Clinical Microbiology, 2003,41(4):1637-1650
86. Humphreys I R, Stewart G R, Turner D J, Patel J, Karamanou D, Snelgrove R J, Young D B. A role for dendritic cells in the dissemination of mycobacterial infection. Microbes and Infection, 2006, 8(5):1339-1346
87. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman R M. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. The Journal of Experimental Medicine, 1992,176(6): 1693-1702
88. Jang S, Uematsu S, Akira S, Salgame P. IL-6 and IL-10 induction from dendritic cells in response to Mycobacterium tuberculosis is predominantly dependent on TLR2-mediated recognition. J Immunol, 2004,173(5):3392-3397
89. Jiao X, Lo-Man R, Guermonprez P, Fiette L, Deriaud E, Burgaud S, Gicquel B, Winter N, Leclerc C. Dendritic cells are host cells for mycobacteria in vivo that trigger innate and acquired immunity. J Immunol, 2002,168(3): 1294-1301
90. Josien R, Wong B R, Li H L, Steinman R M, Choi Y. TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. J Immunol, 1999,162(5):2562-2568
91. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, van Embden J. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. Journal of Clinical Microbiology, 1997,35(4):907-914
92. Khader S A, Partida-Sanchez S, Bell G, Jelley-Gibbs D M, Swain S, Pearl J E, Ghilardi N, Desauvage F J, Lund F E, Cooper A M. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. The Journal of Experimental Medicine, 2006,203(7):1805-1815
93. Lewis K N, Liao R, Guinn K M, Hickey M J, Smith S, Behr M A, Sherman D R. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. The Journal of Infectious Diseases, 2003,187(1):117-123
94. Li L, Bannantine J P, Zhang Q, Amonsin A, May B J, Alt D, Banerji N, Kanjilal S, Kapur V. The complete genome sequence of Mycobacterium avium subspecies paratuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 2005,102(35):12344-12349
95. Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell, 1997, 89(2): 175-184
96. Maeda N, Nigou J, Herrmann J L, Jackson M, Amara A, Lagrange P H, Puzo G, Gicquel B, Neyrolles O. The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. The Journal of Biological Chemistry, 2003,278(8):5513-5516
97. Malowany J I, McCormick S, Santosuosso M, Zhang X, Aoki N, Ngai P, Wang J, Leitch J, Bramson J, Wan Y, Xing Z. Development of cell-based tuberculosis vaccines: genetically modified dendritic cell vaccine is a much more potent activator of CD4 and CD8 T cells than peptide- or protein-loaded counterparts. Molecular Therapy, 2006,13(4):766-775
98. Martino A, Sacchi A, Sanarico N, Spadaro F, Ramoni C, Ciaramella A, Pucillo L P, Colizzi V, Vendetti S. Dendritic cells derived from BCG-infected precursors induce Th2-like immune response. Journal of Leukocyte Biology, 2004, 76(4):827-834
99. Mazars E, Lesjean S, Banuls A L, Gilbert M, Vincent V, Gicquel B, Tibayrenc M, Locht C, Supply P. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. Proceedings of the National Academy of Sciences of the United States of America, 2001,98(4):1901-1906
100.Nerlich A G, Haas C J, Zink A, Szeimies U, Hagedorn H G. Molecular evidence for tuberculosis in an ancient Egyptian mummy. Lancet, 1997, 350(9088):1404
101. O'Brien R, Danilowicz B S, Bailey L, Flynn O, Costello E, O'Grady D, Rogers M. Characterization of the Mycobacterium bovis restriction fragment length polymorphism DNA probe pUCD and performance comparison with standard methods. Journal of Clinical Microbiology, 2000, 38(9):3362-3369
102.Pompei L, Jang S, Zamlynny B, Ravikumar S, McBride A, Hickman S P, Salgame P. Disparity in IL-12 release in dendritic cells and macrophages in response to Mycobacterium tuberculosis is due to use of distinct TLRs. J Immunol, 2007, 178(8):5192-5199
103.Prasad H K, Singhal A, Mishra A, Shah N P, Katoch V M, Thakral S S, Singh D V, Chumber S, Bal S, Aggarwal S, Padma M V, Kumar S, Singh M K, Acharya S K. Bovine tuberculosis in India: potential basis for zoonosis. Tuberculosis (Edinburgh, Scotland), 2005, 85(5-6):421-428
104. Robinson S P, Stagg A J. Dendritic Cell Protocols. Totowa, NJ: Humana Press Inc,2001.191-198
105.Roy E, De Silva A D, Sambandamurthy V K, Clark S O, Stavropoulos E, Jacobs W R, Jr., Brennan J, Chan J, Williams A, Colston M J, Tascon R E. Induction of high levels of protective immunity in mice after vaccination using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. Immunology Letters, 2006, 103(2):196-199
106. Ryan T J, Buddie B M, De Lisle G W. An evaluation of the gamma interferon test for detecting bovine tuberculosis in cattle 8 to 28 days after tuberculin skin testing. Research in Veterinary Science, 2000, 69(1):57-61
107. Schumacher C, Clark-Lewis I, Baggiolini M, Moser B. High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils. Proceedings of the National Academy of Sciences of the United States of America, 1992, 89(21):10542-10546
108. Skuce R A, McCorry T P, McCarroll J F, Roring S M, Scott A N, Brittain D, Hughes S L, Hewinson R G, Neill S D. Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR-PCR targets. Microbiology, 2002, 148(2):519-528
109. Smith NH, Dale J, Inwald J, Palmer S, Gordon SV, Hewinson RG, Smith JM. The population structure of Mycobacterium bovis in Great Britain: clonal expansion. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(25):15271-15275
110. Steinman R M, Cohn Z A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. The Journal of Experimental Medicine, 1973,137(5): 1142-1162
111. Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rusch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez M C, Fauville M, Niemann S, Skuce R, et al. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 2006,44(12):4498-4510
112. Supply P, Lesjean S, Savine E, Kremer K, van Soolingen D, Locht C. Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. Journal of Clinical Microbiology, 2001, 39(10):3563-3571
113. Supply P, Mazars E, Lesjean S, Vincent V, Gicquel B, Locht C. Variable human minisatellite-like regions in the Mycobacterium tuberculosis genome. Molecular Microbiology, 2000, 36(3):762-771
114.Tailleux L, Schwartz O, Herrmann J L, Pivert E, Jackson M, Amara A, Legres L, Dreher D, Nicod L P, Gluckman J C, Lagrange P H, Gicquel B, Neyrolles O. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. The Journal of Experimental Medicine, 2003,197(1): 121-127
115.Tsai H H, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff R M, Miller R H. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell, 2002,110(3):373-383
116. von Meyenn F, Schaefer M, Weighardt H, Bauer S, Kirschning C J, Wagner H, Sparwasser T. Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guerin by Flt3-ligand generated dendritic cells. Immunobiology, 2006, 211(6-8):557-565
117. WHO. World Health Report. 1999. http://www.who.int/whr/1999/report.htm
118.Zganiacz A, Santosuosso M, Wang J, Yang T, Chen L, Anzulovic M, Alexander S, Gicquel B, Wan Y, Bramson J, Inman M, Xing Z. TNF-alpha is a critical negative regulator of type 1 immune activation during Intracellular bacterial infection. The Journal of Clinical Investigation, 2004, 113(3):401-413
119.Zaharik M L, Nayar T, White R, Ma C, Vallance B A, Starke N, Jiang X, Rey-Ladino J, Shen C, Brunham R C. Genetic profiling of dendritic cells exposed to live- or ultraviolet-irradiated Chlamydia muridamm reveals marked differences in CXC chemokine profiles. Immunology, 2007,120(2): 160-172
120. Zhang J, Wang X, Bove K E, Xu M. DNA fragmentation factor 45-deficient cells are more resistant to apoptosis and exhibit different dying morphology than wild-type control cells. The Journal of biological chemistry, 1999,274(52):3 7450-3 7454
121 .Zhang M, Tang H, Guo Z, An H, Zhu X, Song W, Guo J, Huang X, Chen T, Wang J, Cao X. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nature Immunology, 2004, 5(11):1124-1133
122.Zumarraga M J, Martin C, Samper S, Alito A, Latini O, Bigi F, Roxo E, Cicuta M E, Errico F, Ramos M C, Cataldi A, van Soolingen D, Romano M I. Usefulness of spoligotyping in molecular epidemiology of Mycobacterium bovis-related infections in South America. Journal of Clinical Microbiology, 1999, 37(2):296-303
2.蔡宝祥.家畜传染病学第四版.北京:中国农业出版社,2001.
3.陈敬,董德琼,杨渝浩.白介素-12与结核病.国外医学呼吸系统分册,2002,22(4):220-222
4.傅义娟,傅国璋,王生祥.青海省奶牛结核病的调查与防制.中国兽医杂志,2004,40(6):31
5.富立国,王文,赵艳春.奶牛布鲁氏杆菌病、结核病检疫监测的综合措施.黑龙江畜牧兽医,2004,5:77
6.甘海霞,何宝祥,刘棋.牛结核病的危害与流行情况.广西畜牧兽医,2007,23(6):286-288
7.高爱萍,韩方伟,戚磊,段素华.江苏徐州地区奶牛布病、结核病的监测结果与分析.畜牧与兽医,2004,36(5):31-32
8.高建新,谢雪山,陈家军,郑建云,马翔,李忠孝.巍山县奶牛布氏杆菌病、结核病检测的思考.云南畜牧兽医,2005,1:34
9.何邵阳.牛结核病研究进展.预防兽医学研究进展,2001,3(4):34-39
10.黄纪铨.牛结核病.福建畜牧兽医,2000,22(6):39-46
11.黄锦江.广州地区奶牛结核病、布氏病的检疫与防制.广东畜牧兽医科技,1997,22(3):27-28
12.黄瑛,于三科,王建军.新疆昌吉市奶牛结核病、布鲁菌病的检测.动物医学进展,2005,26(10):116-117
13.姬学谦.临夏州奶牛结核病的临测与防制.甘肃畜牧兽医,2004,34(4):18-19
14.吉生宏,祁永秀.西宁市奶牛“两病”监测检疫.畜牧兽医杂志,2005,24(2):34-35
15.季旭仁,金大春,王跃川.瑞安市奶牛结核病监测现状及应对措施.浙江畜牧兽医,2004,2(30
16.孔令萍,罗成波,李建元.兴义市奶牛结核病的调查.贵州畜牧兽医,2003,27(1):11
17.李川,谭亚娣,陈颖钰,胡巧云,马艳,张桂荣,钦博,晁彦杰,陈焕春,郭爱珍.牛IFN-γ原核表达、单克隆抗体制备及其ELISA检测方法的建立.生物工程学报,2007,23(01):40-45
18.李舵,盛卓君,刘进,彭小玲,乔红伟,陈德坤.新疆部分地区牛结核病PPD 监测与分析.动物医学进展,2006,27(4):99-101
19.李积善,许英芬,逮克庆,彭生,晁学元,秦振华,谷玉辉.奶牛结核检测报告.青海畜牧兽医杂志,2003,33(1):46
20.李建玲,陈彪,张婕,王文秀,郭亚军.乌鲁木齐地区奶牛结核病、布鲁氏菌病检疫现状分析与措施.中国食草动物,2005,25(1):37-38
21.李连波,齐梅.牡丹江市奶牛结核病的检疫报告.中国动物检疫,2001,18(6):28-29
22.李晓梅,贺亚雄,沙勇波,韦志芳.一起奶牛结核病的处理与反思.中国兽医杂志,2004,40(3):58-59
23.李业福.奶牛结核病的临测报告.中国兽药杂志,2004,38(6):48-49
24.刘道新,谈志祥,邱立新,鲁杏华,王昌建.湖南省动物布鲁氏菌病和奶牛结核病的调查.湖南畜牧兽医,2003,4:27-28
25.刘思国,王春来,张秀华,郭设平,郭洋,邵美丽.牛结核病病原生态学和流行病学研究.中国畜牧兽医,2005,32(3):60-62
26.刘思国,于辉,宫强.牛结核病研究进展.畜牧兽医科技信息,2003,19(10):10-14
27.陆立权,宋启文,熊毅,磨龙春,郭建刚,何贻坚.广西奶牛结核病和布鲁氏菌病的调查.广西农业科学,1998,2:83-85
28.母安雄,陆永干,应小飞,谷根林,杨宗照,陶益.杭州市奶牛结核病和布氏杆菌病检测结果.浙江畜牧兽医,2003,3:28-29
29.钦博,万学济,胡巧云,喻正军,晁彦杰,郭爱珍,陈焕春,谭亚娣.牛型分枝杆菌MPB70蛋白胶乳凝集方法的建立及应用.中国预防兽医学报.2007,29(01):58-62
30.秦鹏,胡厚如.2005年金安区奶牛结核病的监测结果分析.现代农业科技,2006,5:67
31.全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调 查报告.中华结核和呼吸杂志,2002,25(01):3-7
32.任岩.兰州市西固区奶牛结核病感染调查.中国动物检疫,2003,12:35
33.沈文,张再清,焦忠新,周林,张登海.石河子地区某奶牛场结核病的检疫调查.青海畜牧兽医杂志,2006,36(5):23-24
34.史明基,王建中,刘果,蔡斌.兴化市奶牛结核病的检疫.中国动物检疫,2006,23(2):31-32
35.陶昆,卢贤瑜.肿瘤坏死因子alpha抗结核免疫作用研究进展.国际检验医学杂志,2006,27(2):143-145
36.王明茂,胡祖榕,王孟华,张洪光,蔡传生,吴秀珠.对散养乳牛结核病的普查.福建畜牧兽医,1997,2:33
37.王永康,叶元亨.上海奶牛结核病和布氏杆菌病的控制.乳业科学与技术,2004,3:133-135
38.卫生部.2008年1月全国法定报告传染病疫情.2008.http://www.moh.gov.cn/newshtml/21160.htm
39.吴波,张书环,邓铨涛,项杰,陈军,刘朝,陈鑫,宋念华,陶淑珍,黄继根,韩永佩,赵波,林祥梅,陈焕春,郭爱珍.四种牛分枝杆菌特异性蛋白融合表达及在牛结核病诊断中的临床应用.中国人兽共患病杂志,2007,23(9):41-44
40.吴磊,万庆铭,苏翠萍,杨红.奶牛结核病的普查.四川畜牧兽医,2003,30(3):47
41.吴志仓.永靖县奶牛结核病检疫情况及病原鉴别试验.甘肃畜牧兽医,2001,31(1):10-11
42.吴志明,刘莲芝,李桂喜.动物疫病防治知识.北京:中国农业出版社,2006.
43.肖和平.结核病流行的近期特点.中国临床医生,2004,32(7):2-4
44.肖凌,魏雅稚,夏飞,刘胜武.结核杆菌Hsp65与EGFP融合基因的构建及DC 疫苗的制备.细胞与分子免疫学杂志.2005,21(1):13-16
45.新德,安宁.新疆博乐奶牛结核病调查.新疆畜牧业,2007,1:38-39
46.徐庆,汤碧娥,张志琴.环氧化酶-2的研究进展.中国误诊学杂志,2006,6(19):2705-3707
47.杨家和,钱其军,吴孟超,郭亚军.白介素12:重要的免疫调节因子.世界华人消化杂志,1999,7(1):71-72
48.杨卫冲,焦新安.牛结核病诊断技术研究进展.中国人畜共患病杂志,2004,20(12):1090-1093
49.裔群英,卞红春.盐城地区奶牛结核病和布鲁氏菌病检测及分析.中国动物检疫,2005,22(11):27
50.尹徐凤,李香云,传为军.庆阳县奶牛结核病临测报告.甘肃农村科技,2002,4:18-19
51.应如朗,余全法,鲍伟华,王敏亚,王维金.关于宁波市奶牛结核病的检测报告.浙江畜牧兽医,2001,2:28
52.张桂荣,万学济,陈颖钰,吴波,晁彦杰,吕文,钦博,郭爱珍,陈焕春,谭亚娣.间接ELISA检测牛分枝杆菌抗体方法的建立及初步应用.中国预防兽医学报.2007,29(29):555-560
53.张书环,吴波,曹莎,陈颖钰,晁彦杰,陈焕春,郭爱珍.牛分枝杆菌抗原MPB70、MPB83、CFP-10和ESAT-6的融合表达及相关特性分析.中国人兽共患病学报.2007,23(12):1238-1242
54.张书环,杨俊兴,晁彦杰,颜邦芬,吴波,曹莎,陈颖钰,谭亚娣,陈焕春,郭爱珍.牛结核病抗体胶体金快速检测技术的建立和应用.动物医学进展.2007,28(07):17-24
55.张铁源,康桂花,李华,金正男.前列腺素与非甾体抗炎免疫药.延边医学院学报,1994,17(1):58-61
56.赵国财,祁尚绥,刘学森,宋维军.东营区奶牛结核病检疫报告.中国动物检疫,2001,18(4):37
57.朱长光,李志军,李宏伟.北京市某奶牛场检出结核、副结核阳性牛.中国动物检疫,1999,16(4):19-20
58.Alaniz R C,Sandall S,Thomas E K,Wilson C B.Increased dendritic cell numbers impair protective immunity to intracellular bacteria despite augmenting antigen-specific CD8+ T lymphocyte responses.J Immunol,2004,172(6):3725-3735
59.Aranaz A,Liebana E,Mateos A,Dominguez L,Vidal D,Domingo M,Gonzolez O,Rodriguez-Ferri E F,Bunschoten A E,Van Embden J D,Cousins D.Spacer oligonucleotide typing of Mycobacterium bovis strains from cattle and other animals:a tool for studying epidemiology of tuberculosis.Journal of Clinical Microbiology, 1996,34(11):2734-2740
60. Bafica A, Scanga C A, Feng C G, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. The Journal of Experimental Medicine, 2005, 202(12):1715-1724
61. Bean A G, Roach D R, Briscoe H, France M P, Korner H, Sedgwick J D, Britton W J. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J Immunol, 1999,162(6):3504-3511
62. Behr M A, Wilson M A, Gill W P, Salamon H, Schoolnik G K, Rane S, Small P M. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science, 1999,284(5419): 1520-1523
63. Bodnar K A, Serbina N V, Flynn J L. Fate of Mycobacterium tuberculosis within murine dendritic cells. Infection and Immunity, 2001,69(2):800-809
64. Brosch R, Gordon S V, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald J K, Golby P, Garcia J N, Hewinson R G, Behr M A, Quail M A, Churcher C, Barrell B G, Parkhill J, Cole S T. Genome plasticity of BCG and impact on vaccine efficacy. Proceedings of the National Academy of Sciences of the United States of America, 2007,104(13):5596-5601
65. Brustmann H. DNA fragmentation factor (DFF45): expression and prognostic value in serous ovarian cancer. Pathology, Research and Practice, 2006,202(10):713-720
66. Camus J C, Pryor M J, Medigue C, Cole S T. Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology, 2002,148(Pt 10):2967-2973
67. Cole S T, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon S V, Eiglmeier K, Gas S, Barry C E, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 1998, 393(6685):537-544
68. Cole S T, Eiglmeier K, Parkhill J, James K D, Thomson N R, Wheeler P R, Honore N, Gamier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies R M, Devlin K, Duthoy S, Feltwell T, Fraser A, et al. Massive gene decay in the leprosy bacillus. Nature, 2001,409(6823): 1007-1011
69. Cosivi O, Grange J M, Daborn C J, Raviglione M C, Fujikura T, Cousins D, Robinson R A, Huchzermeyer H F A K, de Kantor I, Meslin F X. Zoonotic Tuberculosis due to Mycobacterium bovis in Developig Countries. Emerging Infectious Diseases. 1998,4(1):59-70
70. Cousins D V, Skuce R A, Kazwala R R, van Embden J D. Towards a standardized approach to DNA fingerprinting of Mycobacterium bovis. International Union Against Tuberculosis and Lung Disease, Tuberculosis in Animals Subsection. Int J Tuberc Lung Dis, 1998,2(6):471-478
71. Cousins D V, Williams S N, Dawson D J. Tuberculosis due to Mycobacterium bovis in the Australian population: DNA typing of isolates, 1970-1994. Int J Tuberc Lung Dis, 1999, 3(8):722-731
72. Cowan L S, Mosher L, Diem L, Massey J P, Crawford J T. Variable-number tandem repeat typing of Mycobacterium tuberculosis isolates with low copy numbers of IS6110 by using mycobacterial interspersed repetitive units. Journal of Clinical Microbiology, 2002,40(5): 1592-1602
73. Demangel C, Bean A G, Martin E, Feng C G, Kamath A T, Britton W J. Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells. European Journal of Immunology, 1999,29(6): 1972-1979
74. Dulphy N, Herrmann J L, Nigou J, Rea D, Boissel N, Puzo G, Charron D, Lagrange P H, Toubert A. Intermediate maturation of Mycobacterium tuberculosis LAM-activated human dendritic cells. Cellular Microbiology, 2007, 9(6): 1412-1425
75. Fleischmann R D, Alland D, Eisen J A, Carpenter L, White O, Peterson J, DeBoy R, Dodson R, Gwinn M, Haft D, Hickey E, Kolonay J F, Nelson W C, Umayam L A, Ermolaeva M, Salzberg S L, Delcher A, Utterback T, Weidman J, Khouri H, et al. Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. Journal of Bacteriology, 2002,184(19):5479-5490
76. Fricke I, Mitchell D, Mirtelstadt J, Lehan N, Heine H, Goldmann T, Bohle A, Brandau S. Mycobacteria induce IFN-gamma production in human dendritic cells via triggering of TLR2. J Immunol, 2006,176(9):5173-5182
77. Frothingham R, Meeker-O'Connell W A. Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology, 1998,144 (Pt 5): 1189-1196
78. Gamier T, Eiglmeier K, Camus J C, Medina N, Mansoor H, Pryor M, Duthoy S, Grondin S, Lacroix C, Monsempe C, Simon S, Harris B, Atkin R, Doggett J, Mayes R, Keating L, Wheeler P R, Parkhill J, Barrell B G, Cole S T, et al. The complete genome sequence of Mycobacterium bovis. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(13):7877-7882
79. Geijtenbeek T B, Van Vliet S J, Koppel E A, Sanchez-Hernandez M, Vandenbroucke-Grauls C M, Appelmelk B, Van Kooyk Y. Mycobacteria target DC-SIGN to suppress dendritic cell function. The Journal of Experimental Medicine, 2003,197(1):7-17
80. Giacomini E, Sotolongo A, Iona E, Severa M, Remoli M E, Gafa V, Lande R, Fattorini L, Smith I, Manganelli R, Coccia E M. Infection of human dendritic cells with a Mycobacterium tuberculosis sigE mutant stimulates production of high levels of interleukin-10 but low levels of CXCL10: impact on the T-cell response. Infection and Immunity, 2006, 74(6):3296-3304
81. Haddad N, Masselot M, Durand B. Molecular differentiation of Mycobacterium bovis isolates. Review of main techniques and applications. Research in Veterinary Science, 2004, 76(1): 1-18
82. Hanekom W A, Mendillo M, Manca C, Haslett P A, Siddiqui M R, Barry C, Kaplan G. Mycobacterium tuberculosis inhibits maturation of human monocyte-derived dendritic cells in vitro. The Journal of Infectious Diseases, 2003,188(2):257-266
83. Henderson R A, Watkins S C, Flynn J L. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J Immunol, 1997, 159(2):635-643
84. Huang Q, Liu D, Majewski P, Schulte L C, Korn J M, Young R A, Lander E S, Hacohen N. The plasticity of dendritic cell responses to pathogens and their components. Science, 2001,294(5543):870-875
85. Huard R C, Lazzarini L C, Butler W R, van Soolingen D, Ho J L. PCR-based method to differentiate the subspecies of the Mycobacterium tuberculosis complex on the basis of genomic deletions. Journal of Clinical Microbiology, 2003,41(4):1637-1650
86. Humphreys I R, Stewart G R, Turner D J, Patel J, Karamanou D, Snelgrove R J, Young D B. A role for dendritic cells in the dissemination of mycobacterial infection. Microbes and Infection, 2006, 8(5):1339-1346
87. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman R M. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. The Journal of Experimental Medicine, 1992,176(6): 1693-1702
88. Jang S, Uematsu S, Akira S, Salgame P. IL-6 and IL-10 induction from dendritic cells in response to Mycobacterium tuberculosis is predominantly dependent on TLR2-mediated recognition. J Immunol, 2004,173(5):3392-3397
89. Jiao X, Lo-Man R, Guermonprez P, Fiette L, Deriaud E, Burgaud S, Gicquel B, Winter N, Leclerc C. Dendritic cells are host cells for mycobacteria in vivo that trigger innate and acquired immunity. J Immunol, 2002,168(3): 1294-1301
90. Josien R, Wong B R, Li H L, Steinman R M, Choi Y. TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. J Immunol, 1999,162(5):2562-2568
91. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, van Embden J. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. Journal of Clinical Microbiology, 1997,35(4):907-914
92. Khader S A, Partida-Sanchez S, Bell G, Jelley-Gibbs D M, Swain S, Pearl J E, Ghilardi N, Desauvage F J, Lund F E, Cooper A M. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. The Journal of Experimental Medicine, 2006,203(7):1805-1815
93. Lewis K N, Liao R, Guinn K M, Hickey M J, Smith S, Behr M A, Sherman D R. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. The Journal of Infectious Diseases, 2003,187(1):117-123
94. Li L, Bannantine J P, Zhang Q, Amonsin A, May B J, Alt D, Banerji N, Kanjilal S, Kapur V. The complete genome sequence of Mycobacterium avium subspecies paratuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 2005,102(35):12344-12349
95. Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell, 1997, 89(2): 175-184
96. Maeda N, Nigou J, Herrmann J L, Jackson M, Amara A, Lagrange P H, Puzo G, Gicquel B, Neyrolles O. The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. The Journal of Biological Chemistry, 2003,278(8):5513-5516
97. Malowany J I, McCormick S, Santosuosso M, Zhang X, Aoki N, Ngai P, Wang J, Leitch J, Bramson J, Wan Y, Xing Z. Development of cell-based tuberculosis vaccines: genetically modified dendritic cell vaccine is a much more potent activator of CD4 and CD8 T cells than peptide- or protein-loaded counterparts. Molecular Therapy, 2006,13(4):766-775
98. Martino A, Sacchi A, Sanarico N, Spadaro F, Ramoni C, Ciaramella A, Pucillo L P, Colizzi V, Vendetti S. Dendritic cells derived from BCG-infected precursors induce Th2-like immune response. Journal of Leukocyte Biology, 2004, 76(4):827-834
99. Mazars E, Lesjean S, Banuls A L, Gilbert M, Vincent V, Gicquel B, Tibayrenc M, Locht C, Supply P. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. Proceedings of the National Academy of Sciences of the United States of America, 2001,98(4):1901-1906
100.Nerlich A G, Haas C J, Zink A, Szeimies U, Hagedorn H G. Molecular evidence for tuberculosis in an ancient Egyptian mummy. Lancet, 1997, 350(9088):1404
101. O'Brien R, Danilowicz B S, Bailey L, Flynn O, Costello E, O'Grady D, Rogers M. Characterization of the Mycobacterium bovis restriction fragment length polymorphism DNA probe pUCD and performance comparison with standard methods. Journal of Clinical Microbiology, 2000, 38(9):3362-3369
102.Pompei L, Jang S, Zamlynny B, Ravikumar S, McBride A, Hickman S P, Salgame P. Disparity in IL-12 release in dendritic cells and macrophages in response to Mycobacterium tuberculosis is due to use of distinct TLRs. J Immunol, 2007, 178(8):5192-5199
103.Prasad H K, Singhal A, Mishra A, Shah N P, Katoch V M, Thakral S S, Singh D V, Chumber S, Bal S, Aggarwal S, Padma M V, Kumar S, Singh M K, Acharya S K. Bovine tuberculosis in India: potential basis for zoonosis. Tuberculosis (Edinburgh, Scotland), 2005, 85(5-6):421-428
104. Robinson S P, Stagg A J. Dendritic Cell Protocols. Totowa, NJ: Humana Press Inc,2001.191-198
105.Roy E, De Silva A D, Sambandamurthy V K, Clark S O, Stavropoulos E, Jacobs W R, Jr., Brennan J, Chan J, Williams A, Colston M J, Tascon R E. Induction of high levels of protective immunity in mice after vaccination using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. Immunology Letters, 2006, 103(2):196-199
106. Ryan T J, Buddie B M, De Lisle G W. An evaluation of the gamma interferon test for detecting bovine tuberculosis in cattle 8 to 28 days after tuberculin skin testing. Research in Veterinary Science, 2000, 69(1):57-61
107. Schumacher C, Clark-Lewis I, Baggiolini M, Moser B. High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils. Proceedings of the National Academy of Sciences of the United States of America, 1992, 89(21):10542-10546
108. Skuce R A, McCorry T P, McCarroll J F, Roring S M, Scott A N, Brittain D, Hughes S L, Hewinson R G, Neill S D. Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR-PCR targets. Microbiology, 2002, 148(2):519-528
109. Smith NH, Dale J, Inwald J, Palmer S, Gordon SV, Hewinson RG, Smith JM. The population structure of Mycobacterium bovis in Great Britain: clonal expansion. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(25):15271-15275
110. Steinman R M, Cohn Z A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. The Journal of Experimental Medicine, 1973,137(5): 1142-1162
111. Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rusch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez M C, Fauville M, Niemann S, Skuce R, et al. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 2006,44(12):4498-4510
112. Supply P, Lesjean S, Savine E, Kremer K, van Soolingen D, Locht C. Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. Journal of Clinical Microbiology, 2001, 39(10):3563-3571
113. Supply P, Mazars E, Lesjean S, Vincent V, Gicquel B, Locht C. Variable human minisatellite-like regions in the Mycobacterium tuberculosis genome. Molecular Microbiology, 2000, 36(3):762-771
114.Tailleux L, Schwartz O, Herrmann J L, Pivert E, Jackson M, Amara A, Legres L, Dreher D, Nicod L P, Gluckman J C, Lagrange P H, Gicquel B, Neyrolles O. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. The Journal of Experimental Medicine, 2003,197(1): 121-127
115.Tsai H H, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff R M, Miller R H. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell, 2002,110(3):373-383
116. von Meyenn F, Schaefer M, Weighardt H, Bauer S, Kirschning C J, Wagner H, Sparwasser T. Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guerin by Flt3-ligand generated dendritic cells. Immunobiology, 2006, 211(6-8):557-565
117. WHO. World Health Report. 1999. http://www.who.int/whr/1999/report.htm
118.Zganiacz A, Santosuosso M, Wang J, Yang T, Chen L, Anzulovic M, Alexander S, Gicquel B, Wan Y, Bramson J, Inman M, Xing Z. TNF-alpha is a critical negative regulator of type 1 immune activation during Intracellular bacterial infection. The Journal of Clinical Investigation, 2004, 113(3):401-413
119.Zaharik M L, Nayar T, White R, Ma C, Vallance B A, Starke N, Jiang X, Rey-Ladino J, Shen C, Brunham R C. Genetic profiling of dendritic cells exposed to live- or ultraviolet-irradiated Chlamydia muridamm reveals marked differences in CXC chemokine profiles. Immunology, 2007,120(2): 160-172
120. Zhang J, Wang X, Bove K E, Xu M. DNA fragmentation factor 45-deficient cells are more resistant to apoptosis and exhibit different dying morphology than wild-type control cells. The Journal of biological chemistry, 1999,274(52):3 7450-3 7454
121 .Zhang M, Tang H, Guo Z, An H, Zhu X, Song W, Guo J, Huang X, Chen T, Wang J, Cao X. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nature Immunology, 2004, 5(11):1124-1133
122.Zumarraga M J, Martin C, Samper S, Alito A, Latini O, Bigi F, Roxo E, Cicuta M E, Errico F, Ramos M C, Cataldi A, van Soolingen D, Romano M I. Usefulness of spoligotyping in molecular epidemiology of Mycobacterium bovis-related infections in South America. Journal of Clinical Microbiology, 1999, 37(2):296-303