Article ; Online: Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection.
2008 Volume 14, Issue 5, Page(s) 558–564
Abstract: ... only poorly understood. We now report that pulmonary interferon-gamma (IFN-gamma) produced during T ... by IFN-gamma neutralization after influenza infection. Direct inoculation of IFN-gamma can mimic ... cell responses to influenza infection in mice inhibits initial bacterial clearance from the lung ...
| 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. |
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| MeSH term(s) | 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/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 ; Interferon gamma Receptor | ||||||||||
| Chemical Substances | CD4 Antigens ; CD8 Antigens ; CD8 antigen, alpha chain ; Complement C3 ; Marco protein, mouse ; Receptors, Immunologic ; Receptors, Interferon ; Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2008-04-27 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural | ||||||||||
| ZDB-ID | 1220066-9 | ||||||||||
| ISSN | 1546-170X ; 1078-8956 | ||||||||||
| ISSN (online) | 1546-170X | ||||||||||
| ISSN | 1078-8956 | ||||||||||
| DOI | 10.1038/nm1765 | ||||||||||
| Shelf mark |
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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