Identification of an innate T helper type 17 response to intestinal bacterial pathogens

被引:196
作者
Geddes, Kaoru [1 ]
Rubino, Stephen J. [2 ]
Magalhaes, Joao G. [1 ]
Streutker, Catherine [3 ]
Le Bourhis, Lionel [1 ]
Cho, Joon Ho [1 ]
Robertson, Susan J. [1 ]
Kim, Connie J. [4 ]
Kaul, Rupert [1 ,4 ]
Philpott, Dana J. [1 ]
Girardin, Stephen E. [2 ]
机构
[1] Univ Toronto, Dept Immunol, Toronto, ON, Canada
[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[3] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada
[4] Univ Toronto, Dept Med, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
ENTERICA SEROTYPE TYPHIMURIUM; INDUCER-LIKE CELLS; HOST-DEFENSE; DENDRITIC CELLS; IL-17; DIFFERENTIATION; INTERLEUKIN-17; INFECTION; EXPRESSION; T(H)17;
D O I
10.1038/nm.2391
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin 17 (IL-17) is a central cytokine implicated in inflammation and antimicrobial defense. After infection, both innate and adaptive IL-17 responses have been reported, but the type of cells involved in innate IL-17 induction, as well as their contribution to in vivo responses, are poorly understood. Here we found that Citrobacter and Salmonella infection triggered early IL-17 production, which was crucial for host defense and was mediated by CD4(+) T helper cells. Enteric innate T helper type 17 (iT(H)17) responses occurred principally in the cecum, were dependent on the Nod-like receptors Nod1 and Nod2, required IL-6 induction and were associated with a decrease in mucosal CD103(+) dendritic cells. Moreover, imprinting by the intestinal microbiota was fully required for the generation of iT(H)17 responses. Together, these results identify the Nod-iT(H)17 axis as a central element in controlling enteric pathogens, which may implicate Nod-driven iT(H)17 responses in the development of inflammatory bowel diseases.
引用
收藏
页码:837 / U202
页数:9
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