Laboratory of Clinical and Experimental Immunology, Infant Center, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, 90610-000, RS, Brazil.
Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, 13083007, São Paulo, Brazil.
Nat Commun. 2019 Jul 22;10(1):3273. doi: 10.1038/s41467-019-11152-6.
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.
严重呼吸道合胞病毒（RSV）感染是 2 岁以下婴儿发病和死亡的主要原因。在这里，我们描述了高纤维饮食可保护小鼠免受 RSV 感染。这种作用依赖于肠道微生物群和醋酸盐的产生。醋酸盐通过增加肺部干扰素刺激基因的表达来介导干扰素-β（IFN-β）反应。这些作用与 RSV 感染小鼠病毒载量和肺部炎症的减少有关。1 型 IFN 通过 IFN-1 受体（IFNAR）信号转导对于肺上皮细胞系中的醋酸盐抗病毒活性以及 RSV 感染小鼠中的醋酸盐保护作用至关重要。肺上皮细胞中 Gpr43 的激活通过 IFN-β 反应降低了病毒诱导的细胞毒性并促进了抗病毒作用。在 Gpr43 小鼠中，醋酸盐对 RSV 感染的作用被消除。我们的研究结果揭示了醋酸盐在肺上皮细胞中通过 IFN-β 发挥抗病毒作用，并涉及 GPR43 和 IFNAR。
