commensal viruses and bacteria

Much attention has been focused on the role of commensal bacteria in health and disease, but the role of commensal viruses is understudied. Metagenomic analysis shows that the intestine of humans and animals harbors various commensal viruses and the dysbiosis is often associated with intestinal infection and inflammatory diseases, but the role and mechanism of commensal viruses in the homeostasis of intestinal immune system remain unexplored. Here, we show that commensal viruses are essential for the homeostasis of intestinal intraepithelial lymphocytes (IELs). The cytosolic viral RNA sensing receptor RIG-I in antigen presenting cells can recognize commensal viruses and maintain IELs via an interferon-independent, but MAVS-IRF1-IL-15 axis dependent manner. Notably, the recovery of IELs restores the colitis susceptibility of commensal viruses-depleted mice to dextran sulfate sodium. Collectively, our results indicate that commensal viruses can support the homeostasis of IELs and regulate mucosal immunity via non-canonical RIG-I signaling.