title: Identification of an innate T helper type 17 response to intestinal bacterial pathogens.
abstract: 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.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rubino
authors.forename: Joao G
authors.initials: JG
authors.lastname: Magalhaes
authors.forename: Catherine
authors.initials: C
authors.lastname: Streutker
authors.forename: Lionel
authors.initials: L
authors.lastname: Le Bourhis
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Robertson
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse