Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation
- PMID: 25366965
- PMCID: PMC4235643
- DOI: 10.1084/jem.20140625
Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation
Erratum in
- J Exp Med. 2014 Dec 15;211(13):2683
- J Exp Med. 2014 Nov 17;211(12):2396-7
Abstract
Influenza in humans is often accompanied by gastroenteritis-like symptoms such as diarrhea, but the underlying mechanism is not yet understood. We explored the occurrence of gastroenteritis-like symptoms using a mouse model of respiratory influenza infection. We found that respiratory influenza infection caused intestinal injury when lung injury occurred, which was not due to direct intestinal viral infection. Influenza infection altered the intestinal microbiota composition, which was mediated by IFN-γ produced by lung-derived CCR9(+)CD4(+) T cells recruited into the small intestine. Th17 cells markedly increased in the small intestine after PR8 infection, and neutralizing IL-17A reduced intestinal injury. Moreover, antibiotic depletion of intestinal microbiota reduced IL-17A production and attenuated influenza-caused intestinal injury. Further study showed that the alteration of intestinal microbiota significantly stimulated IL-15 production from intestinal epithelial cells, which subsequently promoted Th17 cell polarization in the small intestine in situ. Thus, our findings provide new insights into an undescribed mechanism by which respiratory influenza infection causes intestinal disease.
© 2014 Wang et al.
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Comment in
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Mucosal immunology: sick of the flu.Nat Rev Immunol. 2014 Dec;14(12):781. doi: 10.1038/nri3773. Epub 2014 Nov 14. Nat Rev Immunol. 2014. PMID: 25394944 No abstract available.
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FLUshing in the bathroom.J Exp Med. 2014 Nov 17;211(12):2328-9. doi: 10.1084/jem.21112insight4. J Exp Med. 2014. PMID: 25403806 Free PMC article. No abstract available.
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