Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection.
Secondary bacterial infection often occurs after pulmonary virus infection and is a common cause of severe disease in humans, yet the mechanisms responsible for this viral-bacterial synergy in the lung are only poorly understood. We now report that pulmonary interferon-gamma (IFN-gamma) produced during T cell responses to influenza infection in mice inhibits initial bacterial clearance from the lung by alveolar macrophages. This suppression of phagocytosis correlates with lung IFN-gamma abundance, but not viral burden, and leads to enhanced susceptibility to secondary pneumococcal infection, which can be prevented by IFN-gamma neutralization after influenza infection. Direct inoculation of IFN-gamma can mimic influenza infection and downregulate the expression of the class A scavenger receptor MARCO on alveolar macrophages. Thus, IFN-gamma, although probably facilitating induction of specific anti-influenza adaptive immunity, suppresses innate protection against extracellular bacterial pathogens in the lung.
Sun
Keer
K
Center for Immunology & Microbial Disease, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
Metzger
Dennis W
DW
D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D000096743:Interferon gamma Receptor
D015704:CD4 Antigens; D016827:CD8 Antigens; D003176:Complement C3; D007371:Interferon-gamma; D016753:Interleukin-10; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C409469:CD8 antigen, alpha chain; C092228:Marco protein, mouse