ICOSL敲基因小鼠日本血吸虫病模型的免疫应答及其免疫病理(英文)  

Immune response and immunopathology in ICOSL knockout mice infected with Schistosoma japonicum

作　　者：王瑜[1,2] 王波[1] 梁松[1] 龚唯[1] 张惠琴[1] 夏超明[1] 

机构地区：[1]苏州大学医学部病原生物学系,苏州215123 [2]安徽理工大学医学院基础医学系,淮南232001

出　　处：《中国人兽共患病学报》2012年第8期769-775,共7页Chinese Journal of Zoonoses

基　　金：Supported by the National Natural Science Foundation(No.30772027&81171603)~~

摘　　要：目的观察ICOSL敲基因(ICOSL knockout,ICOSL-KO)小鼠感染日本血吸虫后的免疫应答及其免疫病理反应。方法建立ICOSL-KO小鼠及野生型C57BL/6J小鼠日本血吸虫病模型,收集感染前(0周)和感染后(4～20周)的小鼠脾淋巴细胞用SEA进行诱导培养72小时后,采用ELISA双抗夹心法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-10、IL-13)细胞因子表达水平。应用ELISA法检测同期血清中SEA特异性抗体IgG、及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变。结果ICOSL-KO小鼠Th1细胞因子IFN-γ、IL-12表达明显高于野生型小鼠,而其Th2型细胞因子(IL-4、IL-10、IL-13)表达水平却显著低于野生型小鼠。ICOSL-KO小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著低于野生型C57BL/6J小鼠的水平,其Th2分化指数与IgG1/IgG2a的比值亦低于野生型小鼠的水平,特别是在感染7、12、16周后具有显著性差异。且ICOSL-KO小鼠的肝脏虫卵肉芽肿病变显著小于野生型小鼠。结论感染日本血吸虫的ICOSL-KO小鼠Th2免疫应答显著下调并导致肝虫卵肉芽肿病变减弱,表明ICOS–ICOSL信号通路在血吸虫病免疫病理中具有重要作用。To determine immune responses and immunopathology in ICOSL knockout（ICOSL-KO） mice infected with Schistosoma japonicum,ICOSL-KO mice and wild-type C57BL / 6Jmice were used as experimental models for Schistosoma japonicuminfection.The splenic lymphocytes were isolated from the mice the day before infection（0week） as well as 4,7,12,16and 20weeks post-infection,and stimulated with SEA for 72hours in culture.The concentrations of Th1cytokines（IFN-γ and IL-12） and Th2cytokines（IL-4,IL-10and IL-13） in the culture supernatants were measured by sandwich ELISA.The levels of SEA-specific IgG antibody and its subtypes（IgG1and IgG2a） were measured in mouse sera by ELISA.Pathological changes of hepatic granuloma in mice were determined by hematoxylin and eosin（HE） staining.After the infection,the levels of Th1cytokines,IFN-γand IL-12,in ICOSL-KO mice were higher than those in wild-type C57BL / 6Jmice.However,the levels of Th2cytokines（IL-4,IL-10and IL-13） were significantly decreased in ICOSL-KO mice compared to those in wild-type C57BL / 6Jmice.The levels of SEA-specific IgG antibody and its subtypes（IgG1and IgG2a） in the sera of ICOSL-KO mice were also significantly lower than those of wild-type C57BL / 6Jmice.Moreover,the Th2differentiation index was lower in ICOSL-KO mice than in wild-type C57BL / 6J mice at 4,7,12,16and 20 weeks post-infection.Similarly,the ratio of IgG1 / IgG2ain ICOSL-KO mice was significantly lower than that in wild-type C57BL / 6Jmice at 7,12and 16weeks post-infection.Furthermore,throughout the course of disease progression,the volume of hepatic egg granuloma in ICOSL-KO mice was significantly smaller than that in wild-type C57BL / 6Jmice.In conclusions,there is a substantially down-regulated Th2immune response in ICOSL-KO mice infected with Schistosoma japonicum,thus results in an attenuated hepatic lesion caused by egg granulomas.The findings indicate that the ICOS-ICOSL co-stimulatory pathway plays an important role in the hepatic egg granuloma formation of schist

关 键 词：日本血吸虫 肝虫卵肉芽肿 ICOSL敲基因小鼠 ICOS-ICOSL信号通路 TH1/TH2 

分 类 号：R383.2[医药卫生—医学寄生虫学]