Increased IL-17 production in post-septic mice exacerbates respiratory syncytial virus induced immunopathology of the lung (49.25)

Abstract

Abstract Survivors of severe sepsis exhibit increased morbidity and mortality in response to secondary infections. Although bacterial secondary infections have been widely studied, there remains a paucity of data with viral infections post sepsis. Here, we show in an experimental mouse model of severe sepsis (cecal ligation and puncture, CLP) followed by respiratory syncytial virus (RSV) infection, exacerbated immunopathology in the lungs of CLP mice compared to RSV infected sham surgery mice. The immunopathology associated with the viral infection in CLP mice was in part due to increased mucus production in the lungs and impaired ability of septic mice to clear the virus. These findings correlated with increased IL-17 production in the lungs of RSV-infected CLP mice. RSV-infected CLP mice had increased levels of Th2 cytokines and reduced IFNγ in the lungs and lymph nodes compared to RSV infected sham mice. In addition, CD4 T cells from CLP mice ex vivo increased IL-17 production irrespective of the skewing conditions. Further, in vivo neutralization of IL-17 prior to RSV infection led to a significant reduction in virus induced mucus production and Th2 cytokines. Taken together, these data provide evidence that post septic CD4+T cells are primed toward IL-17 production, which may contribute to the immunopathology of a secondary viral infection.