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

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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

Fingerprint

Simian Immunodeficiency Virus
Salmonella
Interleukin-17
Salmonella typhimurium
Viruses
Th17 Cells
Virus Diseases
Interleukin-17 Receptors
Macaca mulatta
Mucosal Immunity
Gene expression
Salmonella Infections
Macaca
Bacteremia
Transcriptome
Gastrointestinal Tract
Mucous Membrane
Defects
HIV
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. / Raffatellu, Manuela; Santos, Renato L.; Verhoeven, David E.; George, Michael D.; Wilson, R. Paul; Winter, Sebastian E.; Godinez, Ivan; Sankaran-Walters, Sumathi; Paixao, Tatiane A.; Gordon, Melita A.; Kolls, Jay K.; Dandekar, Satya; Baumler, Andreas J.

In: Nature Medicine, Vol. 14, No. 4, 04.2008, p. 421-428.

Research output: Contribution to journalArticle

Raffatellu, M, Santos, RL, Verhoeven, DE, George, MD, Wilson, RP, Winter, SE, Godinez, I, Sankaran-Walters, S, Paixao, TA, Gordon, MA, Kolls, JK, Dandekar, S & Baumler, AJ 2008, 'Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut', Nature Medicine, vol. 14, no. 4, pp. 421-428. https://doi.org/10.1038/nm1743
Raffatellu, Manuela ; Santos, Renato L. ; Verhoeven, David E. ; George, Michael D. ; Wilson, R. Paul ; Winter, Sebastian E. ; Godinez, Ivan ; Sankaran-Walters, Sumathi ; Paixao, Tatiane A. ; Gordon, Melita A. ; Kolls, Jay K. ; Dandekar, Satya ; Baumler, Andreas J. / Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. In: Nature Medicine. 2008 ; Vol. 14, No. 4. pp. 421-428.
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