Related Experiment Video
Updated: Jan 7, 2026
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Segmented filamentous bacteria reprogramming of alveolar macrophages limits postinfluenza bacterial pneumonia
Vu L Ngo1,2, Carolin M Lieber1, Hirohito Abo1
1Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta GA 30303, USA.
Abstract:
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.
Insights
Gut bacteria, specifically segmented filamentous bacteria (SFB), reprogram alveolar macrophages (AMs) to prevent depletion and enhance bacterial defense after influenza A virus (IAV) infection. This gut-lung axis protection combats secondary bacterial pneumonia.
Area of Science:
- Immunology
- Microbiology
- Respiratory Medicine
Background:
- Respiratory viral infections, like influenza A virus (IAV), impair alveolar macrophages (AMs), increasing susceptibility to bacterial pneumonia.
- Segmented filamentous bacteria (SFB) colonizing the gut can reprogram AMs, potentially offering protection against secondary infections.
Purpose of the Study:
- To investigate if SFB colonization protects mice against secondary bacterial infections (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) following IAV infection.
- To determine if SFB-induced AM reprogramming is essential and sufficient for this protective effect.
Main Methods:
- Mice were infected with IAV and subsequently challenged with bacteria, with or without prior SFB colonization.
- AM depletion and transplantation experiments were performed to assess the role of AMs.
- Ex vivo analysis of AMs from SFB-colonized mice was conducted to examine epigenetic and functional changes.
Main Results:
- SFB colonization significantly protected mice against secondary bacterial infections by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus after IAV infection, reducing pathogen loads and disease severity.
- AM depletion abrogated SFB-mediated protection, while transplantation of AMs from SFB-colonized mice conferred protection, confirming their necessity and sufficiency.
- Ex vivo analysis showed that SFB reprogrammed AMs to resist IAV-induced depletion and enhanced their bacterial killing capacity through oxidative phosphorylation and complement-dependent phagocytosis, maintaining this phenotype even in an inflamed environment.
Conclusions:
- Gut microbiota composition, particularly SFB, plays a crucial role in modulating host defense against secondary bacterial pneumonia following respiratory viral infections.
- SFB-induced epigenetic reprogramming of AMs enhances their innate immune functions, providing a robust defense mechanism against diverse bacterial pathogens.
- Targeting the gut microbiota represents a potential therapeutic strategy to bolster lung immunity and prevent severe outcomes of co-infections.
