IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection

KF van der Sluijs, LJR van Elden, M Nijhuis… - The Journal of …, 2004 - journals.aai.org
KF van der Sluijs, LJR van Elden, M Nijhuis, R Schuurman, JM Pater, S Florquin…
The Journal of Immunology, 2004journals.aai.org
Secondary pneumococcal pneumonia is a serious complication during and shortly after
influenza infection. We established a mouse model to study postinfluenza pneumococcal
pneumonia and evaluated the role of IL-10 in host defense against Streptococcus
pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally
inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS
(control) on day 0. By day 14 mice had regained their normal body weight and had cleared …
Abstract
Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10 4 CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.
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