Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens

Nat Immunol. 2013 Sep;14(9):937-48. doi: 10.1038/ni.2679. Epub 2013 Aug 4.

Abstract

Defense against attaching-and-effacing bacteria requires the sequential generation of interleukin 23 (IL-23) and IL-22 to induce protective mucosal responses. Although CD4(+) and NKp46(+) innate lymphoid cells (ILCs) are the critical source of IL-22 during infection, the precise source of IL-23 is unclear. We used genetic techniques to deplete mice of specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the attaching-and-effacing pathogen Citrobacter rodentium. We found that the signaling receptor Notch2 controlled the terminal stage of cDC differentiation. Notch2-dependent intestinal CD11b(+) cDCs were an obligate source of IL-23 required for survival after infection with C. rodentium, but CD103(+) cDCs dependent on the transcription factor Batf3 were not. Our results demonstrate a nonredundant function for CD11b(+) cDCs in the response to pathogens in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD11b Antigen / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Citrobacter rodentium / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / mortality
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Interleukin-23 / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Lectins, C-Type / metabolism
  • Lymphotoxin beta Receptor / genetics
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Receptor, Notch2 / deficiency
  • Receptor, Notch2 / metabolism*
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Spleen / immunology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wound Healing / genetics
  • Wound Healing / immunology

Substances

  • Antigens, CD
  • CD11b Antigen
  • DEC-205 receptor
  • Interleukin-23
  • Lectins, C-Type
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Minor Histocompatibility Antigens
  • Receptor, Notch2
  • Receptors, Cell Surface
  • Transcription Factors
  • Zbtb46 protein, mouse