Abstract
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.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
MeSH terms
-
Analysis of Variance
-
Animals
-
Bronchoalveolar Lavage Fluid / cytology
-
Bronchoalveolar Lavage Fluid / immunology
-
CD4 Antigens / genetics
-
CD4 Antigens / immunology
-
CD8 Antigens / genetics
-
CD8 Antigens / immunology
-
Complement C3 / genetics
-
Complement C3 / immunology
-
Enzyme-Linked Immunosorbent Assay
-
Immunity, Innate / drug effects
-
Immunity, Innate / immunology*
-
Interferon gamma Receptor
-
Interferon-gamma / immunology*
-
Interferon-gamma / pharmacology
-
Interleukin-10 / genetics
-
Interleukin-10 / immunology
-
Lung / drug effects
-
Lung / immunology*
-
Macrophages / drug effects*
-
Macrophages / immunology
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Microscopy, Fluorescence
-
Orthomyxoviridae Infections / immunology*
-
Pneumococcal Infections / immunology*
-
Receptors, Immunologic / metabolism
-
Receptors, Interferon / genetics
-
Receptors, Interferon / immunology
Substances
-
CD4 Antigens
-
CD8 Antigens
-
CD8 antigen, alpha chain
-
Complement C3
-
Marco protein, mouse
-
Receptors, Immunologic
-
Receptors, Interferon
-
Interleukin-10
-
Interferon-gamma