PD-1对伯氏疟原虫感染小鼠体液免疫应答的影响

利用伯氏疟原虫Plasmodium berghei ANKA(P.b ANKA)感染BALB/c小鼠,PD-1单抗阻断后,流式细胞术检测脾脏浆细胞、滤泡辅助性T细胞(Tfh)数量。qRT-PCR检测IL-21、IL-10和IL-6 mRNA水平,ELISA检测血清抗体,以探讨程序性死亡受体-1(programmed cell death-1, PD-1)在疟原虫初次感染中对体液免疫应答的影响。结果发现,PD-1单抗阻断加速了P.b ANKA感染小鼠的死亡。与对照组相比,PD-1阻断组感染后第12天短寿浆细胞(CD138~+CD44~+)数量明显降低(P0.05),长寿浆细胞(CD138~+CD44~-、CD138~-CD44~+)和Tfh(CD4~+CXCR5~+)细胞数量无差异性改变,脾细胞IL-21的mRNA水平明显下降(P0.05),血清抗裂殖子表面蛋白(merozoite surface protein, MSP)-1特异性IgG无明显改变。P.b ANKA感染中PD-1通路可能通过影响Tfh分泌IL-21进而干扰浆细胞数量影响体液免疫应答。

Effect of PD-1 on Humoral Immune Response in Plasmodium berghei ANKA Infection

The role of receptor of programmed cell death-1 (PD-1) in humoral immunity in primary infection of malaria was investigated. Plasmodium berghei ANKA (P.b ANKA) infected BALB/c mice was used after blockade of PD 1 monoclonal antibody, and flow cytometry was used to detect the number of long lived and short lived spleen plasma cells, and follicular helper T cells (Tfh). The level of IL-21, IL-10 and IL-6 mRNA was detected by qRT PCR and the level of serum antibodies were detected by ELISA. The results showed that the blockade of PD 1 accelerated the death of P.b ANKA infected mice. As compared with the control group, the number of short lived plasma cells (CD138⁺CD44⁺) was significantly reduced (P<0.05) 12 d after PD-1 blockade of infection, and there was no different changes in the number of longlived plasma cells (CD138⁺CD44⁺) and Tfh (CD4⁺CXCR5⁺), the level of spleen cell IL-21 mRNA of spleen cells was significantly decreased (P<0.05), and the serum of anti specific merozoite surface protein (MSP)-1 specific IgG were not significantly changed. Therefore, PD-1 pathway may affect the number of plasma cells by affecting IL-21 secretion of Tfh, and proceed to affect humoral immune response in P.b ANKA infection.