Co-infection with Plasmodium and chikungunya virus (CHIKV) has been reported in humans, but the impact of co-infection on pathogenesis remains unclear. Here, we show that prior exposure to Plasmodium suppresses CHIKV-associated pathologies in mice. Mechanistically, Plasmodium infection induces IFNγ, which reduces viraemia of a subsequent CHIKV infection and suppresses tissue viral load and joint inflammation. Conversely, concomitant infection with both pathogens limits the peak of joint inflammation with no effect on CHIKV viraemia. Reduced peak joint inflammation is regulated by elevated apoptosis of CD4⁺ T-cells in the lymph nodes and disrupted CXCR3-mediated CD4⁺ T-cell migration that abolishes their infiltration into the joints. Virus clearance from tissues is delayed in both infection scenarios, and is associated with a disruption of B cell affinity-maturation in the spleen that reduces CHIKV-neutralizing antibody production.

中文翻译：

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疟原虫合并感染可预防基孔肯雅病毒引起的病变。


人类中已有疟原虫和基孔肯雅病毒（CHIKV）双重感染的报道，但双重感染对发病机制的影响仍不清楚。在这里，我们表明，预先接触疟原虫可以抑制小鼠的 CHIKV 相关病理。从机制上讲，疟原虫感染会诱导 IFNγ，从而减少随后的 CHIKV 感染的病毒血症并抑制组织病毒载量和关节炎症。相反，两种病原体的同时感染限制了关节炎症的峰值，但对 CHIKV 病毒血症没有影响。关节炎症峰值的减少是通过淋巴结中 CD4 ⁺ T 细胞凋亡增加和破坏 CXCR3 介导的 CD4 ⁺ T 细胞迁移来调节的，从而消除了它们对关节的浸润。在两种感染情况下，病毒从组织中的清除都会延迟，并且与脾脏中 B 细胞亲和力成熟的破坏有关，从而减少 CHIKV 中和抗体的产生。