Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response
Antunes, Krist Helen
Fachi, Jose Luis
de Paula, Rosemeire
da Silva, Emanuelle
Pral, Lais Passariello
dos Santos, Adara Aurea
Dias, Greicy Brisa Malaquias
Vargas, Jose Eduardo
Puga, Renato
Mayer, Fabiana Quoos
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2019-07-22
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-beta (IFN-beta) 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-beta response. The effect of acetate on RSV infection was abolished in Gpr43(-/-) mice. Our findings reveal antiviral effects of acetate involving IFN-beta in lung epithelial cells and engagement of GPR43 and IFNAR.