Accumulated evidences demonstrate that intestinal microbiome can inhibit viral infection. However, our knowledge of the signaling pathways and specific commensal microbes that mediate the antiviral response is limited. Here, a rhabdoviral infection model in zebrafish allows us to investigate the modes of action of microbiome-mediated antiviral effect. We observed that antibiotics-treated and germ-free zebrafish exhibited greater viral infection. Mechanistically, depletion of the intestinal microbiome alters TLR2-Myd88 signaling, and blunts neutrophil response and type I interferon (IFN) production. Moreover, a single commensal bacterium, Cetobacterium somerae, recapitulated TLR2- and type I IFN-dependent antiviral effect of the microbiome in gnotobiotic zebrafish, and C. somerae exopolysaccharides (CsEPS) was the effector molecule that engaged TLR2 to mediate antiviral function. Together, our results suggest a conserved role of intestinal microbiome in regulating type I IFN response among vertebrates, and reveal that the intestinal microbiome inhibits viral infection through a CsEPS-TLR2-type I IFN signaling axis in zebrafish.

The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish