Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response
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Date
2019-07-22
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Communications
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.
Description
Keywords
CHAIN FATTY-ACIDS, GUT MICROBIOTA, DIETARY FIBER, INFLAMMATORY RESPONSES, VIRAL BRONCHIOLITIS, INNATE IMMUNITY, GENE, SUSCEPTIBILITY, CELLS, RSV
Citation
Antunes, K.H., Fachi, J.L., de Paula, R. et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat Commun 10, 3273 (2019). https://doi.org/10.1038/s41467-019-11152-6