2025/01/26 by Vu L. Ngo, Carolin M. Lieber, Hirohito Abo +3 · 1 voice
Immunology and Microbiology · #Immune cells in cancer #Phagocytosis and Immune Regulation
paper · doi:10.1101/2025.01.23.634531
openalex publication_date 2025/01/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14
SUMMARY The most severe outcomes of respiratory viral infection (RVI) result from secondary bacterial infection, which RVI promotes via depletion of alveolar macrophages (AM). Colonization of the intestine by the common but non-ubiquitous commensal, segmented filamentous bacteria (SFB), reprograms AM to resist RVI-induced depletion. Hence, we examined if SFB against secondary infection by S. pneumoniae , H. influenzae , or S. aureus, following primary infection by influenza virus (IAV). Indeed, SFB colonization conferred strong post-IAV protection against these lethal bacterial pathogens. AM depletion and transplant studies indicated that SFB reprogramming these cells was necessary and sufficient for such protection. Assay of AM, ex vivo , from SFB-colonized mice argued their protection against secondary bacterial infection was not only due to their withstanding IAV-induced depletion. Rather, AM from SFB-colonized mice displayed complement-dependent increases in phagocytosis and killing of these bacteria. Furthermore, AM from SFB-colonized mice stably held their enhanced anti-bacterial phenotype even when transplanted into an inflamed interferon-rich post IAV-environment. Thus, SFB, and perhaps gut microbiota composition in general influences proneness to bacterial pneumonia, especially post-RVI. One Sentence summary SFB colonization stably changed the phenotype of alveolar macrophages resulting in sustained clearance of bacterial pathogens even amidst an inflamed interferon-rich immune suppressed lung.