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 (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.
Raffatellu
Manuela
M
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, California 95616-8645, USA.
Santos
Renato L
RL
Verhoeven
David E
DE
George
Michael D
MD
Wilson
R Paul
RP
Winter
Sebastian E
SE
Godinez
Ivan
I
Sankaran
Sumathi
S
Paixao
Tatiane A
TA
Gordon
Melita A
MA
Kolls
Jay K
JK
Dandekar
Satya
S
Bäumler
Andreas J
AJ
D000818:Animals; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000382:microbiology; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000209:etiology / Q000276:immunology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17