Altered Immune Responses in Mice with Concomitant Schistosoma mansoni and Plasmodium chabaudi Infections

Mixed parasitic infections are common in many parts of the world. However, little is known about how concurrent infections affect the immunity to and/or pathogenesis of each other. Protection and elimination of blood-stage Plasmodium chabaudi chabaudi AS in resistant mice are characterized by a sequential activation of CD4(+) Th1 and Th2 cells. The patent egg-laying stage of the murine model of Schistosoma mansoni is associated with a strong Th2 response to both Schistosoma and unrelated antigens. In this study, we investigated how infection of mice with S. mansoni would affect the immune response to and pathogenesis of a P. chabaudi infection. C57BL/6 mice infected with S. mansoni for 8 weeks were infected with blood-stage P. chabaudi. Malaria parasitemias were significantly higher in these mice than in mice infected with P. chabaudi only. In doubly infected mice, both spleen cell proliferative and Th2 responses to S. mansoni soluble egg antigen (SEA) or anti-CD3 were suppressed up to 1 month after the malaria infection. Findings for SEA-specific immunoglobulin M (IgM) and IgG serum antibody levels were similar. No significant effects were seen on P. chabaudi-induced gamma interferon responses. However, tumor necrosis factor alpha (TNF-α) production was significantly lower in double-infected mice. Thus, a defect in TNF-α production might contribute to the increased malaria parasitemias seen in S. mansoni-P. chabaudi-infected mice. Taken together, our data show that schistosoma and malaria infections profoundly affect each other, findings which might have implications for the development of vaccines.

混合寄生虫感染在全球多数地区均较为常见。然而，目前学界对共感染如何相互影响彼此的免疫应答与（或）发病机制仍知之甚少。在抗性小鼠体内，血液期查氏疟原虫查氏亚种AS（Plasmodium chabaudi chabaudi AS）的清除与免疫保护过程，以CD4阳性辅助性T细胞1（Th1）与辅助性T细胞2（Th2）的顺序激活为特征。曼氏血吸虫（Schistosoma mansoni）小鼠模型的显性排卵阶段，与针对曼氏血吸虫及无关抗原的强烈Th2免疫应答密切相关。本研究旨在探究曼氏血吸虫感染如何影响小鼠感染查氏疟原虫后的免疫应答与发病机制。将感染曼氏血吸虫8周的C57BL/6小鼠，再以血液期查氏疟原虫进行攻毒感染。与仅感染查氏疟原虫的小鼠相比，共感染小鼠的疟原虫血症水平显著升高。共感染小鼠中，针对曼氏血吸虫可溶性虫卵抗原（soluble egg antigen, SEA）或抗CD3抗体（anti-CD3）的脾细胞增殖反应与Th2应答，在疟原虫感染后长达1个月的时间内均受到抑制。针对SEA的特异性免疫球蛋白M（immunoglobulin M, IgM）与免疫球蛋白G（immunoglobulin G, IgG）血清抗体水平的检测结果也呈现相似趋势。而查氏疟原虫诱导的γ干扰素（gamma interferon, IFN-γ）应答未受到显著影响。但共感染小鼠的肿瘤坏死因子α（tumor necrosis factor alpha, TNF-α）分泌水平显著降低。因此，肿瘤坏死因子α分泌缺陷可能是曼氏血吸虫-查氏疟原虫共感染小鼠疟原虫血症升高的潜在原因。综上，本研究数据表明，血吸虫感染与疟疾感染可对彼此产生显著影响，该发现或许可为疫苗研发提供新的思路。