CD4+T细胞通过分泌IFN-γ促进伯氏疟原虫红内期感染虫荷的机制研究OA

Objective To investigate the role and mechanism of CD4+T-cell-derived IFN-γ in host defense against blood-stage Plasmodium berghei(P.berghei)infection.Methods A tamoxifen-inducible conditional knockout strategy was performed to generate mice lacking IFN-γ specifically in CD4+T cells(Ifngfl/flCD4-CreERT2).Then after the mice were infected intravenously with luciferase-expressing P.berghei ANKA(P.berghei ANKA-luciferase)strain,parasite burden,survival,and intra-erythrocytic developmental rhythm were monitored dynamically.Flow cytometry and ELISA were carried out respectively to quantify the splenic myeloid subsets and the titers of P.berghei-specific IgG and IgG2c.Results CD4+T-cell-specific IFN-γ deficiency significantly reduced peripheral parasitemia on day 5 post-infection(P<0.05),showing no effect on survival or 24-hour intra-erythrocytic cycle of the parasite.Ifngfl/fl CD4-CreERT2 mice exhibited obviously decreased P.berghei-specific IgG2c(P<0.01)but increased total IgG(P<0.05).Frequencies and absolute numbers of neutrophils,monocytes,and macrophages remained unchanged.Conclusion During the process of P.berghei infection,IFN-γ secreted by CD4+T cells may decrease total serum IgG level by promoting class switching to IgG2c,and then enhance parasite burden after blood-stage P.berghei infection.