A commensal Clostridium species restricts systemic alphavirus dissemination through a type I interferon signaling axis

Abstract

Abstract The role of the gut microbiota in shaping antiviral immune responses at non-intestinal sites has been described in multiple models of viral pathogenesis. Although chikungunya virus (CHIKV), an emerging alphavirus, is a substantial global health threat, the impact of the microbiota in modulating immune responses to alphavirus infection is entirely unexplored. Here, we show that CHIKV infection of oral antibiotic-treated or germ-free mice resulted in increased viremia within one day of infection, and this enhanced viral dissemination. Microbiota depletion resulted in greater CHIKV infection of circulating monocytes, which was linked to dampened systemic type I interferon (IFN) responses. Differences in CHIKV tropism and replication following microbiota depletion depended on MyD88 signaling in plasmacytoid dendritic cells, which contributed to systemic type I IFN production within hours of infection. Colonization of antibiotic-treated mice with a single bacterial microbiota-derived Clostridium species resulted in MyD88-dependent type I IFN responses that restricted CHIKV infection in blood. We propose that select bacterial symbionts impact antiviral immunity to alphaviruses within hours of infection through a type I IFN signaling axis and by virtue of effects on viremia may determine disease severity and affect vector transmission and epidemic spread.