IL-10在感染日本血吸虫p47 GTP酶缺失小鼠中的免疫调节作用  

Immune regulation of IL-10 to Schistosoma japonicum infection in p47 GTPase deficient mouse model

作　　者：吴婧娇[1] 田芳[1] 高雅楠[1] 杜晓棠[1] 张美娟[1] 季旻珺[1] 吴观陵[1] 

机构地区：[1]南京医科大学病原生物学系,南京210029

出　　处：《中国血吸虫病防治杂志》2010年第2期111-116,F0003,共7页Chinese Journal of Schistosomiasis Control

基　　金：国家自然科学基金(30872368)

摘　　要：目的在日本血吸虫早期感染模型和SEA致敏模型中,研究IGTP和IRG-47缺失小鼠在抵抗日本血吸虫感染过程中IL-10的免疫调节作用。方法以IGTP基因敲除(IGTP-/-)小鼠、IRG-47基因敲除(IRG-47-/-)小鼠和野生型(WT)小鼠为研究对象,建立日本血吸虫早期感染模型和可溶性虫卵抗原(SEA)致敏模型。在早期感染模型中,以HE染色观察耳廓的病理变化,间接ELISA法检测耳廓皮片培养上清中Th1/Th2型细胞因子的表达水平;在SEA致敏模型中,以间接ELISA法检测血清中日本血吸虫特异性IgG抗体、脾单个核细胞培养上清中Th1/Th2型细胞因子的表达水平;以及流式细胞术检测脾细胞亚群比例的变化。结果日本血吸虫感染7d后,IGTP-/-、IRG-47-/-和WT小鼠的耳廓病理变化无显著差异;但IRG-47-/-小鼠耳廓培养上清中IL-10水平显著低于IGTP-/-小鼠。SEA致敏小鼠3周后,IGTP-/-小鼠血清中SEA特异性IgG抗体水平显著低于WT小鼠;IRG-47-/-小鼠脾细胞在体外SEA刺激下,产生的IL-10水平显著高于IGTP-/-小鼠和WT小鼠;流式结果显示IRG-47-/-小鼠脾中Th2细胞比例显著低于WT小鼠。结论SEA是IRG-47缺失小鼠抵抗日本血吸虫、促使宿主产生保护性应答的重要调节因素,IL-10在此过程中是重要的免疫调节分子。Objective To investigate the immune response of IL-10 to Schistosoma japonicum infection in the early infectioin model and SEA immunization model of the IGTP-/-and IRG-47-/-mice.Methods In the early infection model,the IGTP knock out （IGTP-/-） mice,IRG-47 knock out （IRG-47^-/-） mice and wild-type （WT） C57BL/6J mice were exposed to 300 S.japonicum cercariae via the pinna and sacrificed on day 7 post-infection.Each mouse pinna section was stained with hematoxylin-eosin （HE） to detect the pathological lesions,and the culture supernatant of pinna was used to test the levels of Th1/Th2 cytokines by indirect ELISA.In the SEA immunization model,IGTP^-/-IRG-47^-/-and WT mice were immunized with SEA twice and sacrificed in 3 weeks after the initial immunization.SEA-specific IgG antibody in sera was detected by indirect ELISA;the levels of Th1/Th2 cytokines were tested in culture supernatant of splenocytes by indirect ELISA;the proportions of CD4^＋ T cells,CD8^＋ T cells,B cells,Th1 and Th2 cells in the spleen were assayed by FACS.Results Although no obvious differences on the pathology of pinna were observed among the three mouse groups,the level of IL-10 in the culture supernatant of pinna of IRG-47^-/-mice was lower than that of IGTP^-/-mice in 7 days after the exposure.Following SEA immunization,the level of SEA-specific IgG antibody in sera of IGTP^-/-mice was lower than that in WT mice,the level of IL-10 in the culture supernatant of splenocytes of IRG-47^-/-mice was higher than that of IGTP^-/-and WT mice with the stimulation of SEA.However,the proportion of Th2 cells in the spleen of IRG-47^-/-mice was the lowest among the three mouse groups.Conclusions SEA is the stimulus of IRG-47 deficiency mice to defend Schistosoma japanicum infection and promote the host to produce a protective response,and IL-10 may play an important role in immune regulation in this process.

关 键 词：日本血吸虫 p47GTP酶 免疫调节 IL-10 基因敲除 小鼠 

分 类 号：R383.24[医药卫生—医学寄生虫学]