Influenza-induced expression of indoleamine 2,3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia

Airway infection with influenza virus induces local expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which has been shown to enhance inflammatory mediator responses in vitro. Because secondary pneumococcal infections occurring shortly after recovery from influenza...

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Vydáno v:	The Journal of infectious diseases Ročník 193; číslo 2; s. 214
Hlavní autoři:	van der Sluijs, Koenraad F, Nijhuis, Monique, Levels, Johannes H M, Florquin, Sandrine, Mellor, Andrew L, Jansen, Henk M, van der Poll, Tom, Lutter, René
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 15.01.2006
Témata:	Animals Bronchoalveolar Lavage Fluid - cytology Delayed-Action Preparations - administration & dosage Delayed-Action Preparations - pharmacology Disease Models, Animal Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - pharmacology Female Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Influenza A virus Interleukin-10 - analysis Interleukin-10 - biosynthesis Lung - immunology Lung - microbiology Mice Mice, Inbred C57BL Orthomyxoviridae Infections - complications Orthomyxoviridae Infections - enzymology Orthomyxoviridae Infections - immunology Pneumonia, Pneumococcal - etiology Pneumonia, Pneumococcal - immunology Pneumonia, Pneumococcal - microbiology Streptococcus pneumoniae - growth & development Streptococcus pneumoniae - immunology Survival Analysis Tryptophan - administration & dosage Tryptophan - analogs & derivatives Tryptophan - pharmacology Tumor Necrosis Factor-alpha - analysis
ISSN:	0022-1899
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Shrnutí:	Airway infection with influenza virus induces local expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which has been shown to enhance inflammatory mediator responses in vitro. Because secondary pneumococcal infections occurring shortly after recovery from influenza are associated with enhanced inflammatory responses, we hypothesized that IDO activity contributes to the enhanced response to bacterial challenges in mice previously infected with influenza virus. On day 14 after influenza virus infection (with strain A/PR/8/34), C57Bl/6 mice were intranasally inoculated with 1 x 10(4) colony-forming units of S. pneumoniae (serotype 3). Matrix-driven delivery pellets that contained 70 mg of the IDO inhibitor 1-methyl-DL-tryptophan (MeTrp) released over a period of 7 days were subcutaneously implanted 48 h before pneumococcal infection. MeTrp treatment resulted in a 20-fold reduction in pneumococcal outgrowth 48 h after bacterial inoculation. Remarkably, pulmonary levels of interleukin-10 and tumor necrosis factor-alpha were significantly reduced in mice treated with MeTrp. Our data suggest that IDO expression during influenza virus infection alters the inflammatory response and facilitates the outgrowth of pneumococci during secondary bacterial pneumonia.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1899
DOI:	10.1086/498911