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Viruses in our gut—friend or foe?
▸ Yang JY, Kim MS, Kim E, et al. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production. Immunity 2016;44: 889–900.
Gut homeostasis is regulated by complex interactions between genetic and environmental factors and the host's immune system. When this homeostasis is disrupted, gut inflammation ensues. Microbial imbalance, also known as dysbiosis, plays a critical role in intestinal pathology; however, previous studies have only focused on commensal bacteria despite metagenomic studies revealing that a variety of resident viruses inhabit the healthy gut. What role do these resident viruses play in regulating intestinal homeostasis and how do these viruses interact with the host innate immune system? A recent study by Yang and colleagues sheds light on these questions. The researchers found that treating mice with an antiviral cocktail before dextran sulfate sodium (DSS) treatment resulted in more severe colitis compared with untreated mice. Antiviral treatment led to reduced viral particles and community-wide changes in resident gut viral DNA and RNA metagenomes. Treatment of wild-type mice with Toll-like receptor 3 (TLR3) or TLR7 agonists and inactivated rotavirus improved symptoms, and Tlr3−/− and Tlr7−/− mice were more susceptible to DSS-induced colitis. Treatment with TLR3+7 agonists resulted in an increase of IFN-β production by plasmacytoid dendritic cells isolated from inflamed mouse colon. The role of enteric virus signalling at onset and disease severity of IBD in humans was investigated by analysing the associations of human TLR3 and TLR7 variants and susceptibility to IBD using direct sequencing and genotyping of the two gene variants. Their results suggest that the TLR3+7-mediated host defence mechanism plays an indispensable role in gut inflammation regulation. In summary, these findings demonstrate that resident gut viruses reduce inflammation via secretion of IFN-β in a TLR3+7-dependent manner. Until now, intestinal viruses were regarded as harmful …