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Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut.
- Source :
-
Nature medicine [Nat Med] 2008 Apr; Vol. 14 (4), pp. 421-8. Date of Electronic Publication: 2008 Mar 23. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Female
Humans
Ileum immunology
Ileum microbiology
Immunity, Mucosal
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
Simian Acquired Immunodeficiency Syndrome complications
T-Lymphocytes, Helper-Inducer immunology
Interleukin-17 deficiency
Intestinal Mucosa immunology
Intestinal Mucosa microbiology
Salmonella typhimurium pathogenicity
Simian Acquired Immunodeficiency Syndrome immunology
Simian Acquired Immunodeficiency Syndrome microbiology
Simian Immunodeficiency Virus pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 18376406
- Full Text :
- https://doi.org/10.1038/nm1743