Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense

Immunity. 2012 Feb 24;36(2):276-87. doi: 10.1016/j.immuni.2011.12.011. Epub 2012 Feb 2.

Abstract

Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIIIγ. Systemic administration of flagellin, a bacterial protein that stimulates Toll-like receptor 5 (TLR5), induces epithelial expression of RegIIIγ and protects mice from intestinal colonization with antibiotic-resistant bacteria. Flagellin-induced RegIIIγ expression is IL-22 dependent, but how TLR signaling leads to IL-22 expression is incompletely defined. By using conditional depletion of lamina propria dendritic cell (LPDC) subsets, we demonstrated that CD103(+)CD11b(+) LPDCs, but not monocyte-derived CD103(-)CD11b(+) LPDCs, expressed high amounts of IL-23 after bacterial flagellin administration and drove IL-22-dependent RegIIIγ production. Maximal expression of IL-23 subunits IL-23p19 and IL-12p40 occurred within 60 min of exposure to flagellin. IL-23 subsequently induced a burst of IL-22 followed by sustained RegIIIγ expression. Thus, CD103(+)CD11b(+) LPDCs, in addition to promoting long-term tolerance to ingested antigens, also rapidly produce IL-23 in response to detection of flagellin in the lamina propria.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD11b Antigen / metabolism
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Flagellin / administration & dosage
  • Flagellin / immunology*
  • Immunity, Innate
  • Immunity, Mucosal
  • Integrin alpha Chains / metabolism
  • Interleukin-22
  • Interleukin-23 / biosynthesis*
  • Interleukin-23 / deficiency
  • Interleukin-23 / genetics
  • Interleukins / biosynthesis
  • Interleukins / deficiency
  • Interleukins / genetics
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreatitis-Associated Proteins
  • Proteins / genetics
  • Signal Transduction / immunology
  • Toll-Like Receptor 5 / deficiency
  • Toll-Like Receptor 5 / genetics
  • Toll-Like Receptor 5 / metabolism
  • Up-Regulation

Substances

  • Antigens, CD
  • CD11b Antigen
  • Integrin alpha Chains
  • Interleukin-23
  • Interleukins
  • Membrane Proteins
  • Pancreatitis-Associated Proteins
  • Proteins
  • Reg3g protein, mouse
  • Toll-Like Receptor 5
  • alpha E integrins
  • flt3 ligand protein
  • Flagellin