Title: Commensal Microbiota Modulation of Natural Resistance to Virus Infection
Author: Kailyn L. Stefan, Myoungjoo V. Kim, Akiko Iwasaki, Dennis L. Kasper
Abstract: Interferon (IFN)-Is are crucial mediators of antiviral immunity and homeostatic immunesystem regulation. However, the source of IFN-I signaling under homeostatic conditionsis unclear. We discovered that commensal microbes regulate the IFN-I response throughinduction of IFN-β by colonic DCs. Moreover, the mechanism by which a specific commensalmicrobe induces IFN-β was identified. Outer membrane (OM)-associated glycolipids ofgut commensal microbes belonging to the Bacteroidetes phylum induce expression of IFN-β. Using Bacteroides fragilis and its OM-associated polysaccharide A, we determined that IFN-β expression was inducedvia TLR4-TRIF signaling. Antiviral activity of this purified microbial molecule againstinfection with either vesicular stomatitis virus (VSV) or influenza was demonstratedto be dependent on the induction of IFN-β. In a murine VSV infection model, commensal-inducedIFN-β regulated natural resistance to virus infection. Due to the physiological importanceof IFN-Is, discovery of an IFN-β-inducing microbial molecule represents a potentialapproach for the treatment of some human diseases.