C5aR基因缺失小鼠对局部L.major感染的抵抗作用

发布时间：2018-01-13 17:09

本文关键词：C5aR基因缺失小鼠对局部L.major感染的抵抗作用　出处：《南华大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：研究C5a/C5aR通路对BALB/c小鼠局部L.major感染敏感性的影响及对CD4+T细胞免疫应答的调节作用。方法：经皮下注射对各受试组小鼠脚掌进行感染；利用电子卡尺每周定时监测受感染脚掌与未感染脚掌病损厚度之差，观察比较野生型BALB/c和C5aR基因缺失小鼠在不同剂量L.major感染后的病损变化；利用有限稀释法检测了各组感染小鼠体内寄生虫的负荷；在常规剂量（1×10~6/mouse）L.major感染条件下，，使用ELISA法检测受试小鼠受引流淋巴结细胞体外重刺激培养上清中CD4+Th1相关细胞因子IFN-γ的浓度，并进一步通过ELISA和FACS检测了CD4+Th1及Th2相关细胞因子IL-17和IL-4的产生。结果：在常规剂量(1×10~6/mouse) L.major感染条件下，C5aR基因缺失小鼠感染L.major后的病损程度与感染部位寄生虫负荷均显著低于野生型BALB/c小鼠，但在高剂量(5×10~6/mouse)感染条件下，上述指标在两组小鼠间无明显差异；ELISA结果显示细胞因子IFN-γ的产生在感染后的C5aR基因缺失与野生型小鼠间无显著差异；FACS胞内染色结果表明感染后的C5aRKO小鼠CD4+IL-4+T细胞亚群百分比显著低于野生型BALB/c小鼠感染组，但CD3+IL-17+T细胞亚群的百分比在两组之间无显著差异。结论：1. C5a/C5aR信号通路在常规剂量(1×10~6/mouse) L.major感染条件下，可介导野生型BALB/c小鼠对L.major的敏感性，而缺失C5aR基因阻断这一通路有助于降低感染程度；但当L.major剂量达到5×10~6/mouse时，C5aR基因缺失与否对感染程度没有影响。 2. C5a/C5aR信号通路在L.major感染的BALB/c小鼠中可能主要通过调节Th2细胞因子IL-4的产生，进而诱导Th2免疫应答的分化，加剧易感小鼠的L.major受感染部位的病损程度。
[Abstract]:Objective : To study the effect of C5a / C5a1pathway on the sensitivity of local L . major infection in BALB / c mice and its effect on the immune response of CD4 + T cells . Methods : The levels of CD4 + Th1 - related cytokines IL - 17 and IL - 4 were detected by ELISA and FACS . The levels of CD4 + Th1 - related cytokines IFN - 纬 were detected by ELISA and FACS . Results : Under the condition of normal dose ( 1 脳 10 ~ 6 / mouse ) L . major infection , there was no significant difference between the severity of the disease and the parasitic load of the infected site . The results showed that the percentage of CD4 + IL - 4 + T cells in the infected C5aRKO mice was significantly lower than that of wild - type BALB / c mice . The results showed that the percentage of CD4 + IL - 4 + T cells in the infected C5aRKO mice was significantly lower than that of wild type BALB / c mice . Conclusion : 1 . The C5a / C5a1signal pathway can mediate the susceptibility of wild - type BALB / c mice to L . major in the normal dose ( 1 脳 10 ~ 6 / mouse ) L . Major infection conditions , while the deletion of C5a1gene blocks this pathway to reduce the degree of infection . However , when the major dose of L . major reaches 5 脳 10 ~ 6 / mouse , the deletion of C5a1gene has no effect on the degree of infection . 2 . In BALB / c mice infected with L . major infection , C5a / C5a1signal pathway may mainly regulate the production of Th2 cytokine IL - 4 , thus inducing differentiation of Th2 immune response and increasing the degree of disease damage in L . major infected part of susceptible mice .

【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R392

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