Document Detail


STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung.
MedLine Citation:
PMID:  23042197     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 TH2 cytokines and reduced interferon γ 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 TH2 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.
Authors:
Sumanta Mukherjee; Ronald M Allen; Nicholas W Lukacs; Steven L Kunkel; William F Carson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  38     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-03-11     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  515-23     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Female
Gene Expression Regulation / genetics,  immunology
Interferon-gamma / biosynthesis,  genetics,  immunology
Interleukin-17 / biosynthesis*,  genetics,  immunology
Lung / immunology,  metabolism*,  pathology,  virology
Mice
Mice, Inbred BALB C
Respiratory Syncytial Virus Infections / genetics,  immunology,  metabolism*,  pathology
Respiratory Syncytial Viruses*
STAT3 Transcription Factor / genetics,  immunology,  metabolism*
Sepsis / genetics,  immunology,  metabolism*,  pathology
Th2 Cells / immunology*,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
R01 AI073876/AI/NIAID NIH HHS; R01 HL031237/HL/NHLBI NIH HHS; R01AI073876-03/AI/NIAID NIH HHS; R01HL031237-27/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-17; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; 82115-62-6/Interferon-gamma
Comments/Corrections

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