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-Walters, Tatiane A. Paixao, Melita A. Gordon, Jay K. Kolls, Satya Dandekar, Andreas J Baumler

Research output: Contribution to journalArticle

413 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)
  • Medicine(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-Walters, S., Paixao, T. A., Gordon, M. A., Kolls, J. K., Dandekar, S., & Baumler, 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