Enteric Viruses Ameliorate Gut Inflammation via TLR3 and TLR7-mediated Interferon-beta Production

Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis is associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor (TLR) 3/7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. In addition, mice deficient in both TLR3 and TLR7, which lack the ability to recognize viral single- and double-stranded RNAs, were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3/7 genetic variations significantly influenced the severity of ulcerative colitis. Of important, plasmacytoid DCs isolated from inflamed mouse colon produced interferon- in a TLR3/7-dependent manner. These results imply that recognition of resident viruses by TLR3/7 might be required for protective immunity during gut inflammation.