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Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice.

Authors: Kudva, A  Scheller, EV  Robinson, KM  Crowe, CR  Choi, SM  Slight, SR  Khader, SA  Dubin, PJ  Enelow, RI  Kolls, JK  Alcorn, JF 
Citation: Kudva A, etal., J Immunol. 2011 Feb 1;186(3):1666-74. Epub 2010 Dec 22.
Pubmed: (View Article at PubMed) PMID:21178015
DOI: Full-text: DOI:10.4049/jimmunol.1002194

Staphylococcus aureus is a significant cause of hospital and community acquired pneumonia and causes secondary infection after influenza A. Recently, patients with hyper-IgE syndrome, who often present with S. aureus infections of the lung and skin, were found to have mutations in STAT3, required for Th17 immunity, suggesting a potential critical role for Th17 cells in S. aureus pneumonia. Indeed, IL-17R(-/-) and IL-22(-/-) mice displayed impaired bacterial clearance of S. aureus compared with that of wild-type mice. Mice challenged with influenza A PR/8/34 H1N1 and subsequently with S. aureus had increased inflammation and decreased clearance of both virus and bacteria. Coinfection resulted in greater type I and II IFN production in the lung compared with that with virus infection alone. Importantly, influenza A coinfection resulted in substantially decreased IL-17, IL-22, and IL-23 production after S. aureus infection. The decrease in S. aureus-induced IL-17, IL-22, and IL-23 was independent of type II IFN but required type I IFN production in influenza A-infected mice. Furthermore, overexpression of IL-23 in influenza A, S. aureus-coinfected mice rescued the induction of IL-17 and IL-22 and markedly improved bacterial clearance. These data indicate a novel mechanism by which influenza A-induced type I IFNs inhibit Th17 immunity and increase susceptibility to secondary bacterial pneumonia.

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RGD Object Information
RGD ID: 5147404
Created: 2011-08-03
Species: All species
Last Modified: 2011-08-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.