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

Nat Med. 2008 Apr;14(4):421-8. doi: 10.1038/nm1743. Epub 2008 Mar 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Humans
  • Ileum / immunology
  • Ileum / microbiology
  • Immunity, Mucosal
  • Interleukin-17 / deficiency*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / genetics
  • Salmonella Infections, Animal / etiology
  • Salmonella Infections, Animal / immunology
  • Salmonella typhimurium / pathogenicity*
  • Simian Acquired Immunodeficiency Syndrome / complications
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / microbiology*
  • Simian Immunodeficiency Virus / pathogenicity*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin-17