16S data from CHIKV infected mice under various antibiotic treatments.
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.