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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。
Objective To investigate the regulatory mechanism of Listeria monocytogenes (Lm) on immune response in mice infected with lethal Plasmodium yoelii 17XL (P.y 17XL). Methods Mice were inoculated with Lm and heat-killed Lm (HKLm) into the tail vein 2 days after intraperitoneal injection of Plasmodium falciparum. The control group was infected with Plasmodium alone and the mice were treated with paralysis and survival rate. The mice were sacrificed after infection, cytokines IFN-γ in spleen cells were detected by flow cytometry, the levels of IL-4, IL-10, IL-12p40 and IFN-γ were detected by Real-time PCR and spleen cells were detected by Griess reaction Supernatant in the nitric oxide (NO) content. Results Compared with the control group, the level of paralysis in the Lm vaccination group was significantly decreased. On the 5th day after P.y 17XL infection, the levels of IFN-γ secreted by CD4 + and CD8 + T cells were significantly increased, while the macrophages were activated and NO production was increased. Three days after P.y17XL infection (1 d after Lm), the level of IFN-γ in Lm vaccinated group was significantly higher than that in HKLm vaccinated group, and the level of paraminosis in HKLm vaccinated group was basically the same as that in control group. Conclusion This study shows that Lm can enhance the immunity of Th1 response to malaria infection in mice infected with P.y 17XL, and this protective effect is related to the induction of IFN-γ secretion in early stage of infection. This is of great scientific significance for further development of anti-malarial drugs using Lm as a vaccine carrier or adjuvant.