Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemin
Author: ["Manuela Raffatellu","Renato L Santos","David E Verhoeven","Michael D George","R Paul Wilson","Sebastian E Winter","Ivan Godinez","Sumathi Sankaran","Tatiane A Paixao","Melita A Gordon","Jay K Kolls","Satya Dandekar","Andreas J Bäumler"]
Publication: Nature Medicine
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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.
Cite this article
Raffatellu, M., Santos, R., Verhoeven, D. et al. Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 14, 421–428 (2008). https://doi.org/10.1038/nm1743
