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

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 (T(H)17) 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 T(H)17 responses, including the expression of interleukin- 17 (IL- 17) and IL- 22. T(H)17 cells were markedly depleted in SIV- infected rhesus macaques, resulting in blunted T(H)17 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.