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

Krist Helen AntunesJosé Luís FachiRosemeire de PaulaEmanuelle Fraga da SilvaLaís Passariello PralAdara Áurea Dos SantosGreicy Brisa Malaquias DiasJosé Eduardo VargasRenato D PugaFabiana Quoos MayerFábio MaitoCarlos R Zárate-BladésNadim J AjamiMarcella Ramos Sant'AnaThamiris CandrevaHosana Gomes RodriguesMarcio SchmieleMaria Teresa Pedrosa Silva ClericiJosé Luiz Proença-ModenaAngélica Thomas VieiraCharles R MackayDaniel Santos MansurMauricio T CaballeroJacqui MarzecJianying LiXuting WangDouglas BellFernando P PolackSteven R KleebergerRenato T SteinMarco Aurélio Ramirez VinoloAna Paula Duarte de Souza
Published in: Nature communications (2019)
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.
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