A commensal Clostridium species restricts alphavirus dissemination through a bile acid-type I IFN signaling axis. 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.