Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Manuela Raffatellu, Renato L. Santos, David E. Verhoeven, Michael D. George, R. Paul Wilson, Sebastian E. Winter, Ivan Godinez, Sumathi Sankaran, Tatiane A. Paixao, Melita A. Gordon, Jay K. Kolls, Satya Dandekar, Andreas J. Bäumler

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417 Scopus citations

Abstract

Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by TH17 responses, including the expression of interleukin-17 (IL-17) and IL-22. TH17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted TH17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor-deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)421-428
Number of pages8
JournalNature medicine
Volume14
Issue number4
DOIs
StatePublished - Apr 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Raffatellu, M., Santos, R. L., Verhoeven, D. E., George, M. D., Wilson, R. P., Winter, S. E., Godinez, I., Sankaran, S., Paixao, T. A., Gordon, M. A., Kolls, J. K., Dandekar, S., & Bäumler, A. J. (2008). Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nature medicine, 14(4), 421-428. https://doi.org/10.1038/nm1743