Resistance To Local Infection With L.major In C5aR Gene Knock-out Mice

Objective: To study the role of C5a/C5aR pathway in L.major infection and CD4+T cellimmune response in BALB/c mice.Methods: Mice were infected with L.major by subcutaneous infusion. The developmentand progression of footpad lesions in C5aR gene knock-out mice and wild type mice weremonitored weekly by measuring the thickness difference between infected and uninfectedcontralateral feet with electronic calipers. Parasites proliferation in vivo was quantified bylimiting dilution analysis. The cultural supernatant Th1cells related cytokine IFN-gammaof infected draining lymph nodes in each subject mice were measured by ELISA,respectively. The level of Th2cells subpopulation related cytokine IL-4andproinflammatory cytokine IL-17were measured by FACS.Results: When infected with L.major at dosage of1×10~6/mouse, C5aRKO mice showedresistance to the infection and the parasites burden was significantly lower than wild typemice. The intracellular expression of Th2cytokine IL-4in C5aRKO mice was significantlower than that of wild type mice. However, the level of IL-17was not significantlydifferent between wild type and C5aR KO mice. When infected with L.major at dosage of5×10~6/mouse, there are no differences in lesions’ parameters between C5aRKO and wildtype mice.Conclusion:1. C5a/C5aR pathway may promote the lesion development in miceinfected with L.major. Knocking-out of C5aR can alleviate the infection of L.major atconventional dosage (1×10~6/mouse), but shows no effect at higher dosage of5×10~6/mouse.2. C5a/C5aR pathway may mediate the lesions progressing through promotingTh2-cell responses and up-regulating Th2cytokine IL-4.