Details

Autor(en) / Beteiligte

• Ngo, Vu L.
• Lieber, Carolin M.
• Kang, Hae-ji
• Sakamoto, Kaori
• Kuczma, Michal
• Plemper, Richard K.
• Gewirtz, Andrew T.

Titel

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

Ist Teil von

• Cell host & microbe, 2024-03, Vol.32 (3), p.335-348.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Gut microbiota composition influences severity of respiratory viral infection•Gut-restricted segmented filamentous bacteria reprograms lung macrophages•Expression levels of complement and Notch4 expression impact viral infection severity•Transplant of lung macrophages transfers proneness to respiratory viral infection Ngo, Lieber, and colleagues report that colonization of the intestine by segmented filamentous bacteria reprograms lung macrophages conferring them with enhanced ability to combat respiratory viruses, resulting in ameliorated disease. These findings demonstrate the potential of gut microbiome to influence the severity of respiratory viral infection via influencing lung macrophages.