Interferon (IFN)-Is are crucial mediators of antiviral immunity and homeostatic immune system regulation. However, the source of IFN-I signaling under homeostatic conditions is unclear. We discovered that commensal microbes regulate the IFN-I response through induction of IFN-β by colonic DCs. Moreover, the mechanism by which a specific commensal microbe induces IFN-β was identified. Outer membrane (OM)-associated glycolipids of gut 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 induced via TLR4-TRIF signaling. Antiviral activity of this purified microbial molecule against infection with either vesicular stomatitis virus (VSV) or influenza was demonstrated to be dependent on the induction of IFN-β. In a murine VSV infection model, commensal-induced IFN-β regulated natural resistance to virus infection. Due to the physiological importance of IFN-Is, discovery of an IFN-β-inducing microbial molecule represents a potential approach for the treatment of some human diseases.

干扰素（IFN）-Is是抗病毒免疫和稳态免疫系统调节的关键介质。但是，在稳态条件下IFN-1信号的来源尚不清楚。我们发现，共生微生物通过结肠DCs诱导IFN-β来调节IFN-I反应。此外，确定了特定共生微生物诱导IFN-β的机制。属于门生拟杆菌的肠道共生微生物的外膜（OM）相关糖脂诱导IFN-β的表达。使用脆弱的拟杆菌和它的OM相关多糖A，我们确定IFN-β表达是通过TLR4-TRIF信号传导诱导的。已证明这种纯化的微生物分子对水疱性口炎病毒（VSV）或流感病毒感染的抗病毒活性取决于IFN-β的诱导。在鼠VSV感染模型中，共生诱导的IFN-β调节了对病毒感染的天然抗性。由于IFN-β的生理重要性，发现诱导IFN-β的微生物分子代表了治疗某些人类疾病的潜在方法。