16S data from CHIKV infected mice under various antibiotic treatments.. A commensal Clostridium species restricts alphavirus dissemination through a bile acid-type I IFN signaling axis

Although the emerging alphavirus, chikungunya virus (CHIKV) has infected millions of people globally, the factors modulating disease outcome remain poorly understood. Here, we show that oral antibiotic-treated or germ-free mice sustain greater CHIKV infection within one day of virus inoculation. Microbiota depletion leads to blunted systemic production of type I interferon (IFN), which is linked to altered MyD88 signaling in plasmacytoid dendritic cells (pDCs). As a result, circulating monocytes express fewer IFN-stimulated genes and sustain higher levels of CHIKV infection. We identified a single commensal bacterial species, Clostridium scindens, and its derived metabolite, the secondary bile acid deoxycholic acid, that were capable of restoring MyD88-dependent type I IFN responses to restrict systemic CHIKV infection. Thus, commensal gut bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects virus dissemination.

尽管新兴甲病毒属病毒基孔肯雅病毒（chikungunya virus, CHIKV）已在全球范围内造成数百万人群感染，但目前对调控其疾病转归的相关分子机制仍知之甚少。本研究发现，经口服抗生素处理的小鼠以及无菌小鼠，在病毒接种后1天内，体内基孔肯雅病毒的感染负荷显著升高。菌群耗竭会导致全身性I型干扰素（IFN）的生成受阻，这一现象与浆细胞样树突状细胞（pDCs）内MyD88信号通路的异常改变密切相关。因此，循环单核细胞中干扰素刺激基因的表达水平显著下调，其体内的基孔肯雅病毒感染负荷也随之升高。本研究鉴定出一种共生细菌——解聚多糖梭菌（Clostridium scindens），及其代谢产物次级胆汁酸脱氧胆酸，二者均可恢复MyD88依赖性I型干扰素应答，从而抑制全身性基孔肯雅病毒感染。综上，肠道共生菌可通过胆汁酸-pDC-IFN信号轴，在感染后数小时内调控宿主的抗病毒免疫功能以及循环甲病毒的载量，进而影响病毒的播散过程。