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 pro

liferation in vivo was quantified by limiting dilution analysis. Levels of Th2 cells subpopulation related cytokine 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 (P0.05) and parasites load were both significantly reduced (6.952±0.398 vs 4.340±0.434

P0.01). 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 0.314 0±0.042 6

P0.01)

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 0.858 0±0.084 5

P=0.5223).       Conclusion       C5a/C5aR pathway plays a critical role in regulation of mice susceptible to L. major infection via promoting IL-4 production.