Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response.

ABSTRACT: 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-? (IFN-?) 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-? response. The effect of acetate on RSV infection was abolished in Gpr43-/- mice. Our findings reveal antiviral effects of acetate involving IFN-? in lung epithelial cells and engagement of GPR43 and IFNAR.

SUBMITTER: Antunes KH 

PROVIDER: S-EPMC6646332 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature