Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection.

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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AMs). In SFB-negative mice, AMs were quickly depleted as RVI progressed. In contrast, AMs from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AMs from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AMs 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. Copyright © 2024 Elsevier Inc. All rights reserved.

Citation

Vu L Ngo, Carolin M Lieber, Hae-Ji Kang, Kaori Sakamoto, Michal Kuczma, Richard K Plemper, Andrew T Gewirtz. Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection. Cell host & microbe. 2024 Mar 13;32(3):335-348.e8

Mesh Tags

Substances

PMID: 38295788

search → result