Ngo Vu L, Lieber Carolin M, Kang Hae-Ji, Sakamoto Kaori, Kuczma Michal, Plemper Richard K, Gewirtz Andrew T
bioRxiv. 2024 Jan 13:2023.09.21.558814. doi: 10.1101/2023.09.21.558814.
Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and SARS-CoV-2, was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AM). In SFB-negative mice, AM were quickly depleted as RVI progressed. In contrast, AM from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AM from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AM into SFB-free hosts recapitulated SFB-mediated protection against IAV. These findings uncover complex interactions that mechanistically link the intestinal microbiota with AM functionality and RVI severity.
Intestinal segmented filamentous bacteria reprogram alveolar macrophages promoting nonphlogistic defense against respiratory viruses.
个体对呼吸道病毒感染（RVI）的易感性差异很大。由于肠道微生物群会影响免疫功能，我们研究了肠道微生物群组成对RVI的影响，并确定自然获得或外源性给予的分节丝状菌（SFB）可保护小鼠免受流感病毒（IAV）感染。这种保护作用也适用于呼吸道合胞病毒和SARS-CoV-2，它独立于干扰素和适应性免疫，但需要常驻的肺泡巨噬细胞（AM）。在SFB阴性小鼠中，随着RVI的进展，AM会迅速耗竭。相比之下，来自SFB定植小鼠的AM在本质上发生了改变，以抵抗IAV诱导的耗竭和炎症信号传导。然而，来自SFB定植小鼠的AM并非静止不动。相反，它们通过增强补体产生和吞噬作用直接使IAV失活。因此，将SFB转化的AM转移到无SFB的宿主中可重现SFB介导的对IAV的保护作用。这些发现揭示了复杂的相互作用，从机制上将肠道微生物群与AM功能和RVI严重程度联系起来。
肠道分节丝状菌重新编程肺泡巨噬细胞，促进对呼吸道病毒的非炎症防御。
