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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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 193; no. 2; p. 214
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 15.01.2006
Subjects:
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
Online Access:Get more information
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Summary: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.
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ISSN:0022-1899
DOI:10.1086/498911