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

Publication date: Jan 23, 2024

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.

Concepts Keywords
Coronavirus complement
Intestinal gut-lung axis
Mice inflammatory anergy
Microbiome influenza
Severe macrophages
phagocytosis
segmented filamentous bacteria

Semantics

Type Source Name
disease MESH viral infection
disease IDO susceptibility
disease MESH influenza
disease MESH infection
disease VO Respiratory syncytial virus
disease VO Severe acute respiratory syndrome coronavirus 2
disease IDO production

Original Article

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