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 journalArticlepeer-review

425 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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