C5a/C5aR通路在硕大利什曼原虫易感小鼠免疫病理发生中的作用及其机制

Role of C5a/C5aR pathway in immunopathogenesis of mice susceptible to L. major infection and its mechanism

目的研究C5a/C5aR通路在对硕大利什曼原虫(Leishmania major,L.major)易感的BALB/c小鼠免疫病理发生中的作用及机制探讨。方法以C5aR KO小鼠(BALB/c背景)为模型,观察比较了WT和C5aR KO的BALB/c小鼠在L.major感染后的病变情况,有限稀释法检测了各组感染小鼠体内寄生虫的负荷,并进一步通过FACS检测了相关细胞因子如IL-17和IL-4的产生,来探讨C5a/C5aR通路在L.major易感型BALB/c小鼠免疫病理发生中的作用机制。结果相比WT小鼠,C5aRKO小鼠感染L.major后的病变程度明显减轻(P<0.05),体内寄生虫负荷也显著降低(6.952±0.398vs 4.340±0.434,P<0.01);同时,FACS胞内染色结果表明CD4+IL-4+T细胞亚群百分比显著降低(0.960 0±0.148 3 vs0.314 0±0.042 6,P<0.01),但CD3+IL-17+T细胞亚群的百分比在两组之间无显著差异(0.792 0±0.051 3 vs 0.858 0±0.084 5,P=0.522 3)。结论 C5a/C5aR通路通过调节Th2细胞关键细胞因子IL-4的产生,在L.major易感小鼠的免疫病理发生中发挥作用。

Objective To study the role of C5a/C5aR pathway in immunopathogenesis of mice susceptible to Leishmania major （L. major） infection, and to investigate its mechanism. Methods C5aR knock out （KO） BALB/c mice were used as animal models, and wild type （WT） BALB/c mice were used as controls. Development and progress of footpad lesion was monitored weekly by measuring the lesion size after infection. Parasites proliferation in vivo was quantified by limiting dilution analysis. Levels of Th2 cells subpopulation related eytokine IL-4 and proinflammatory cytokine IL-17 were measured by FACS. Results Compared with WT mice, C5aR KO mice became highly resistant to L. major infection as their lesion degree （ P 〈 0.05 ） and parasites load were both significantly reduced （6. 952 ± 0. 398 vs 4. 340 ± 0.434, P 〈 0.01 ）. The percentage of CD4 ± IL-4 ＊ T cell subset in the C5aR KO mice was significantly lower than that in the WT mice （0. 960 0 ±0. 148 3 vs O. 314 0 ± 0. 042 6, P 〈 0.01 ）, but there was no significant difference between the percentages of CD3 ＋ IL-17 ＋ T cell subset in C5aR KO mice and WT mice （0. 792 0 ±0.051 3 vs O. 858 0 ± 0.084 5, P = 0. 5223）. Conclusion C5a/C5aR pathway plays a critical role in regulation of mice suscepti- ble to L. major infection via promoting IL-4 production.