Journal Article

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

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

2019

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 140/58 / 45/77 / 49/23 / 49/31 / 631/250 / 631/250/262 / 631/326/41 / 631/326/596 / 64/60 / 82/51 / 96/106 / 96/21 / A549 Cells / Acetates - metabolism / Acetates - pharmacology / Acetic acid / Animals / Antiviral activity / Cell Line / Cell lines / Chlorocebus aethiops / Cytotoxicity / Epithelial cells / Gene expression / Humanities and Social Sciences / Humans / Infant mortality / Infants / Infections / Interferon / Interferon Type I - metabolism / Intestinal microflora / Intestine / Lung - drug effects / Lung - metabolism / Lung - virology / Lungs / Mice, Inbred C57BL / Mice, Knockout / Microbiota / Morbidity / multidisciplinary / Oral administration / Polymorphism, Single Nucleotide / Protective Agents - metabolism / Protective Agents - pharmacology / Receptor, Interferon alpha-beta - genetics / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Respiratory syncytial virus / Respiratory Syncytial Virus Infections - genetics / Respiratory Syncytial Virus Infections - prevention & control / Respiratory Syncytial Virus Infections - virology / Science / Science (multidisciplinary) / Toxicity / Vero Cells / Viral Load - drug effects / Viral Load - genetics / Viruses / β-Interferon