Intestinal microbiomes are of vital importance in antagonizing systemic viral infection. However, very little literature has shown whether commensal bacteria play a crucial role in protecting enteric virus systemic infection from the aspect of modulating host innate immunity. Also, only a few specific commensal bacteria species have been revealed to be capable in regulating antiviral innate immune responses mediated by type I interferon (IFN). The underlying mechanisms have not yet been elucidated.
We utilized an enteric virus, encephalomyocarditis virus (EMCV) to inoculate PBS-treated or antibiotic cocktail-administrated mice (Abx) orally or intraperitoneally to examine the impact of microbiota depletion on virulence and viral replication in vivo. Microbiota depletion exacerbated the mortality, neuropathogenesis, viremia and viral burden in brain following EMCV infection. Furthermore, Abx-treated mice exhibited severely diminished macrophage activation and impaired type I IFN production and ISG expression in PBMC, spleen or brain. With the help of fecal bacterial 16S rRNA sequencing of PBS and Abx mice, we identified a single commensal bacterium Blautia coccoides (B. coccoides) that can restore macrophage- and IFNAR-dependent type I IFN responses to restrict systemic enteric virus infection.
Our present study demonstrates that intestinal microbiome is fundamental for protecting from enteric virus systemic infection through activating macrophages and type I IFN responses. Reconstitution with B. coccoides can inhibit enteric virus infection and mitigate its neuropathogenesis by activating IFN-I and ISG responses in macrophages via IFNAR- and STAT1-mediated signaling pathway.