Article ; Online: Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and ROS production.
The Journal of infectious diseases
2014 Volume 209, Issue 11, Page(s) 1827–1836
Abstract: ... form of post-influenza pneumonia, and increasing staphylococcal drug resistance makes the development ... by alveolar macrophages and neutrophils, and was associated with increased production of reactive oxygen species (ROS ... Seasonal and especially pandemic influenza predispose patients to secondary bacterial ...
| Abstract | Seasonal and especially pandemic influenza predispose patients to secondary bacterial pneumonias, which are a major cause of deaths and morbidity. Staphylococcus aureus is a particularly common and deadly form of post-influenza pneumonia, and increasing staphylococcal drug resistance makes the development of new therapies urgent. We explored an innate immune-mediated model of the lung to define novel mechanisms by which the host can be protected against secondary staphylococcal pneumonia after sub-lethal influenza infection. We found that stimulating the innate immunity in the lung by overexpression of GM-CSF will result in resistance to S. aureus pneumonia after sublethal influenza infection. Resistance was mediated by alveolar macrophages and neutrophils, and was associated with increased production of reactive oxygen species (ROS) by alveolar macrophages. Resistance was abrogated by treatment with agents that scavenged ROS. We conclude that stimulating innate immunity in the lung markedly reduces susceptibility to post-influenza staphylococcal pneumonia and that this may represent a novel immunomodulatory strategy for prevention and treatment of secondary bacterial pneumonia after influenza. |
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| MeSH term(s) | Amphiregulin ; Animals ; Gene Expression Regulation/immunology ; Glycoproteins/genetics ; Glycoproteins/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Influenza A Virus, H1N1 Subtype ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Macrophages, Alveolar ; Neutrophils ; Orthomyxoviridae Infections/complications ; Orthomyxoviridae Infections/microbiology ; Orthomyxoviridae Infections/virology ; Phagocytes/physiology ; Pneumonia, Staphylococcal/complications ; Pneumonia, Staphylococcal/microbiology ; Reactive Oxygen Species/metabolism ; Staphylococcus aureus | ||||||||||
| Chemical Substances | Amphiregulin ; Glycoproteins ; Intercellular Signaling Peptides and Proteins ; Reactive Oxygen Species ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2014-06-01 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3019-3 | ||||||||||
| ISSN | 1537-6613 ; 0022-1899 | ||||||||||
| ISSN (online) | 1537-6613 | ||||||||||
| ISSN | 0022-1899 | ||||||||||
| DOI | 10.1093/infdis/jit830 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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