Segmented filamentous bacteria reprogramming of alveolar macrophages limits postinfluenza bacterial pneumonia

Respiratory viral infection induces depletion and dysfunction of alveolar macrophages (AMs), resulting in high-susceptibility to life-threatening bacterial pneumonia. Colonization of the intestine by segmented filamentous bacteria (SFB) reprograms AM to resist depletion. Hence, we examined whether SFB protected mice against secondary bacterial infection by Streptococcus pneumoniae , Haemophilus influenzae , or Staphylococcus aureus after influenza A virus (IAV) infection. SFB protected mice against these infections based on pathogen loads and disease symptoms. AM depletion and transplant indicated that SFB-induced AM reprogramming was necessary and sufficient for such protection. Ex vivo analysis revealed that AMs from SFB-colonized mice not only resisted IAV-induced depletion but also were epigenetically reprogrammed to preferentially use oxidative phosphorylation and complement-dependent phagocytosis, which enabled efficient killing of bacteria. AM from SFB-colonized mice held their enhanced antibacterial phenotype even when transplanted into an inflamed interferon-rich post–IAV environment. Thus, gut microbiota composition influences susceptibility to bacterial pneumonia, especially after respiratory viral infection.