Balb／c小鼠PD-1敲除后抑制疟原虫生长及其机制初探

The effect of PD-1 on the course of P.y17XL infection and the underlining mechanism

目的探讨PD-1 KO(knock out)对约氏疟原虫P.y17XL增殖的影响及其可能的作用机制。方法感染约氏疟原虫P.y17XL后,比较WT和PD-1 KO小鼠的存活率及其体内的原虫血症;然后,流式细胞技术检测约氏疟原虫P.y17XL感染能否诱导WT小鼠巨噬细胞、DC、中性粒细胞和活化的CD4+T细胞表面PD-1表达;最后比较感染约氏疟原虫P.y17XL的WT和PD-1 KO小鼠的脾脏CD4+T细胞功能以及血清中的抗体水平。结果与WT小鼠相比,PD-1 KO小鼠的疟原虫增殖明显受到抑制,而且存活率也明显高于感染的WT小鼠;约氏疟原虫P.y17XL感染能诱导WT小鼠巨噬细胞、DC、中性粒细胞和CD4+T细胞表面PD-1的表达;虽然WT和PD-1 KO小鼠的脾脏CD4+T细胞功能没有显著差别,但是PD-1 KO小鼠的血清总IgG水平在感染后第6、8天显著高于WT小鼠。结论 PD-1 KO后能提高感染小鼠的存活率,增强其清除红内期疟原虫的能力;其机制可能与PD-1 KO小鼠血清中抗体水平升高有一定的关系。

This study aimed to investigate the effect of PD-1 on the course of the P.yl7XL infection, and the underlining mechanism. We firstly compared both the survival rate and parasitemia of the PD-1 KO mice with those of WT. Then, the expression of PD-1 on DCs, macrophages, neutrophils and malaria-specific CD4＋T cells of WT mice was analyzed. Furthermore, both CD4＋T activation and serum antibody level of the PD-1 KO mice was compared with those of WT mice at 0, 2, 4, 6, and 8 days after infection with P.yl7XL. We found that the parasitemia of PD-1 KO mice was much lower than that of WT mice at 6 days after infection with P.yl7XL, and survival rate of PD-1 KO mice was much higher than that of WT mice after infection with P.yl7XL. FACS analysis showed that infection of P.yl7XL could induce the expression of PD-1 on DCs, neutrophils and activated CD4＋T cells. Although IFN-γ-secretion and proliferation capacity of CD4＋T ceils of PD-1 KO mice were comparable to those of WT mice, a higher level of total IgG was found in PD-1 KO mice than that in WT mice at 6 and 8 days post infection. From all the result, we get a conclusion that the deficiency of PD-1 could enhance the capacity of mice to clear the malaria parasite and increase the survival rate of the infected mice, which might be related to the higher level of total IgG in the PD-1 knock out mice.