Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-β (IFN-β) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-β response. The effect of acetate on RSV infection was abolished in Gpr43 − / − mice. Our findings reveal antiviral effects of acetate involving IFN-β in lung epithelial cells and engagement of GPR43 and IFNAR. Dietary fibers and SCFAs can exert a protective effect against respiratory syncytial virus (RSV). Here, the authors report that microbiota-derived acetate protects mice against RSV infection via GPR43- mediated type 1 interferon response induction in the lungs.
【저자키워드】 immunology, Virology, Innate immunity, Bacteria, 【초록키워드】 Infection, lung, cytotoxicity, antiviral activity, pulmonary inflammation, Antiviral effect, microbiota, Viral load, respiratory syncytial virus, RSV, mice, Lungs, morbidity and mortality, receptor, expression, protective effect, Acetate, oral administration, pulmonary epithelial cell, reduction, IFN-β, IFNAR, interferon-stimulated gene, Effect, type 1 interferon, intestinal, PROTECT, reduced, dependent on, Type, lung epithelial cell, promoted, Dietary fiber, SCFA, 【제목키워드】 Infection, respiratory syncytial virus, interferon response, Acetate, PROTECT,