TY - JOUR
T1 - Influenza-induced expression of indoleamine 2,3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia
AU - Van Der Sluijs, Koenraad F.
AU - Nijhuis, Monique
AU - Levels, Johannes H M
AU - Florquin, Sandrine
AU - Mellor, Andrew L.
AU - Jansen, Henk M.
AU - Van Der Poll, Tom
AU - Lutter, René
PY - 2006/1/15
Y1 - 2006/1/15
N2 - Background. 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. Methods. On day 14 after influenza virus infection (with strain A/PR/8/34), C57B1/6 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. Results. 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-α were significantly reduced in mice treated with MeTrp. Conclusions. Our data suggest that IDO expression during influenza virus infection alters the inflammatory response and facilitates the outgrowth of pneumococci during secondary bacterial pneumonia.
AB - Background. 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. Methods. On day 14 after influenza virus infection (with strain A/PR/8/34), C57B1/6 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. Results. 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-α were significantly reduced in mice treated with MeTrp. Conclusions. 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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U2 - 10.1086/498911
DO - 10.1086/498911
M3 - Article
C2 - 16362885
AN - SCOPUS:30944440041
SN - 0022-1899
VL - 193
SP - 214
EP - 222
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -