Influenza‐Induced Expression of Indoleamine 2,3‐Dioxygenase Enhances Interleukin‐10 Production and Bacterial Outgrowth during Secondary Pneumococcal Pneumonia

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Abstract
BackgroundAirway 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 MethodsOn day 14 after influenza virus infection (with strain A/PR/8/34), C57Bl/6 mice were intranasally inoculated with 1×104 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 ResultsMeTrp 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–α were significantly reduced in mice treated with MeTrp ConclusionsOur 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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