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

Nat Med. 2011 Jun 12;17(7):837-44. doi: 10.1038/nm.2391.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citrobacter rodentium / immunology
  • Colitis / immunology
  • Colitis / microbiology
  • Enterobacteriaceae Infections / immunology
  • Female
  • Immunity, Innate / immunology
  • Interleukin-17 / immunology
  • Interleukin-6 / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestines / immunology
  • Intestines / microbiology*
  • Male
  • Mice
  • Nod1 Signaling Adaptor Protein / immunology
  • Nod2 Signaling Adaptor Protein / immunology
  • Salmonella Infections, Animal / immunology
  • Salmonella typhimurium / immunology
  • Th17 Cells / immunology*

Substances

  • Interleukin-17
  • Interleukin-6
  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse