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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11152-6

2041-1723

Krist Helen Antunes, José Luís Fachi, Rosemeire de Paula, Emanuelle Fraga da Silva, Laís Passariello Pral, Adara A. Santos, Greicy Brisa Malaquias Dias, José Eduardo Vargas, Renato Puga, Fabiana Quoos Mayer, Fábio Luiz Dal Moro Maito, Carlos R. Zárate-Bladés, Nadim J. Ajami, Marcella Ramos Sant’Ana, Thamiris Candreva, Hosana Gomes Rodrigues, Márcio Schmiele, Maria Teresa Pedrosa Silva Clerici, José Luiz Proença‐Módena, Angélica T. Vieira, Charles R. Mackay, Daniel Santos Mansur, Mauricio T. Caballero, Jacqui Marzec, Jianying Li, Xuting Wang, Douglas A. Bell, Fernando P. Polack, Steven R. Kleeberger, Renato T. Stein, Marco Aurélio Ramirez Vinolo, Ana Paula Duarte de Souza,

Gut microbiota and health

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.