李斯特菌上调约氏疟原虫感染鼠疟模型的Th1应答效应  

Listeria monocytogenes infection upregulates Th1 response in the mouse model of blood- stage Plasmodium yoelii infection

作　　者：韩雪[1] 张娅琳 赵国明[1] 杨冀[1] 祁赞梅[1] 

机构地区：[1]中国医科大学免疫教研室,沈阳110001 [2]宜昌市疾病预防与控制中心病检所,443000

出　　处：《免疫学杂志》2014年第6期474-478,共5页Immunological Journal

基　　金：辽宁省社会发展攻关计划(2013225303)

摘　　要：目的探讨李斯特菌(Listeria monocytogenes,Lm)对致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y 17XL)感染小鼠的免疫应答调节机制。方法小鼠腹腔注射感染疟原虫2 d后尾静脉分别接种Lm及热灭活李斯特菌(heat-killed Lm,HKLm),对照组单独感染疟原虫,统计小鼠虫血症及生存率。感染后处死小鼠,流式细胞术检测脾细胞内细胞因子IFN-γ,Real-time PCR检测细胞因子IL-4、IL-10、IL-12p40、IFN-γ分泌水平,Griess反应检测脾细胞上清中一氧化氮(NO)含量。结果与对照组相比,Lm接种组的虫血症水平明显降低,P.y 17XL感染后5 d,CD4+、CD8+T细胞分泌的IFN-γ水平明显升高,巨噬细胞活化,NO产生增加。P.y17XL感染后3 d(Lm接种后1 d),Lm接种组比HKLm接种组IFN-γ水平升高显著,HKLm接种组虫血症水平与对照组基本一致。结论本研究表明Lm通过增强P.y 17XL感染小鼠的Th1应答对疟疾感染起到一定的免疫保护作用,并且这种保护作用与感染早期诱导IFN-γ分泌有关。这对于进一步以Lm为疫苗载体或佐剂研制抗疟新药具有重要的科学指导意义。This study designed to investigate the immune regulation effect of Listeria monocytogenes （Lm） inoculation on blood-stage Plasmodium yoelii 17XL （P.y 17XL） infection in C57BL/6 mice. Mice were inoculated with Lm or HKLm （Heat-killed Lm） 2 days after they were infected intraperitoneally with plasmodium. Then parasitemia and survival rate were monitored everyday. The levels of IFN-γ IL-4, IL-10 and IL-12p40 in the spleen were determined by realtime PCR, while the level of NO was detected by Griess reaction. We found that Lm inoculation significantly decreased the parasitemia in mice infected with P.y 17XL. The IFN-γ production of CD4＋ and CD8＋ T cells in Lm-inoculated group were higher than those of control group. The levels of CD11b＋ macrophages and NO in Lm-infected group were higher than those of control group. Mice administered with live Lm had a profound production of IFN-γ at day 3 after P.y 17XL infection. However, mice inoculated with HKLm could not generate a similar response. Our results suggested that Lm infection can protect mice against blood-stage Plasmodium yoelii infection by enhancing Thl response, and pointed out the importance of early stage IFN-γ production in inducing the protective immune response.

关 键 词：约氏疟原虫 李斯特菌 TH1免疫应答 IFN-Γ 

分 类 号：R392[医药卫生—免疫学]