Journal
SHOCK
Volume 38, Issue 5, Pages 515-523Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0b013e31826f862c
Keywords
Inflammation; infection; mucus; cytokines; lymphocytes
Funding
- National Institutes of Health [R01AI073876-03, R01HL031237-27]
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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 concerning viral infections after sepsis. In an experimental mouse model of severe sepsis (cecal ligation and puncture [CLP]) followed by respiratory syncytial virus (RSV) infection, exacerbated immunopathology was observed in the lungs of CLP mice compared with RSV-infected sham surgery mice. This virus-associated immunopathology was evidenced by increased mucus production in the lungs of RSV-infected CLP mice and correlated with increased IL-17 production in the lungs. Respiratory syncytial virus-infected CLP mice exhibited increased levels of T(H)2 cytokines and reduced interferon gamma in the lungs and lymph nodes compared with RSV-infected sham mice. In addition, CD4 T cells from CLP mice produced increased IL-17 in vitro irrespective of the presence of exogenous cytokines or blocking antibodies. This increased IL-17 production correlated with increased STAT3 transcription factor binding to the IL-17 promoter in CD4 T cells from CLP mice. Furthermore, in vivo neutralization of IL-17 before RSV infection led to a significant reduction in virus-induced mucus production and T(H)2 cytokines. Taken together, these data provide evidence that postseptic CD4(+) T cells are primed toward IL-17 production via increased STAT3-mediated gene transcription, which may contribute to the immunopathology of a secondary viral infection.
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