Dietary mannose improves antiviral immunity of zebrafish by enriching Cetobacterium somerae

Mannose is a natural monosaccharide with multiple beneficial effects. However, the effect of mannose on the antiviral immunity of hosts has yet to be explored. Here we investigated the antiviral function of dietary mannose and elucidated the microbiota-associated mechanism in a zebrafish model. Dietary mannose at 0.5% increased survival of zebrafish following SVCV challenge. Consistently, mannose supplementation enhanced type I IFN antiviral immunity of zebrafish post viral infection. The antiviral effect of mannose was eliminated in zebrafish fed an antibiotic cocktail or in germ-free (GF) zebrafish, indicating a dependence on the intestinal microbiota. In particular, dietary mannose specifically improved the abundance of Cetobacterium somerae in the intestine of zebrafish, and the antiviral effect of mannose in gnotobiotic zebrafish depended on the colonization of Cetobacterium somerae . Consistent with the mode of action of Cetobacterium somerae , knockdown of type I IFN receptors, TLR2, and Myd88 in zebrafish larvae blocked the antiviral effect of mannose. Lastly, dietary mannose enriched gut Cetobacterium somerae , protecting largemouth bass from largemouth bass virus (LMBV) infection, suggesting that the effect of mannose can be extended to economically valuable fish species. Together, our results show that dietary mannose protects against viral infection in zebrafish by specifically promoting the abundance of gut Cetobacterium somerae , which enhances antiviral immunity via the TLR2-type I IFN signaling pathway.