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J Immunol. 2011 Feb 1;186(3):1666-1674. doi: 10.4049/jimmunol.1002194. Epub 2010 Dec 22.

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

Author information

1
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224.
2
Department of Genetics, Lousiana State University Health Sciences Center, New Orleans, LA 70112.
3
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756.
#
Contributed equally

Abstract

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.

PMID:
21178015
PMCID:
PMC4275066
DOI:
10.4049/jimmunol.1002194
[Indexed for MEDLINE]
Free PMC Article

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