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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigens, CD / metabolism
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CD11b Antigen / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Citrobacter rodentium / immunology*
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Enterobacteriaceae Infections / immunology
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Enterobacteriaceae Infections / microbiology
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Enterobacteriaceae Infections / mortality
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Host-Pathogen Interactions / genetics
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Host-Pathogen Interactions / immunology
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Interleukin-23 / metabolism
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / microbiology
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Lectins, C-Type / metabolism
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Lymphotoxin beta Receptor / genetics
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Lymphotoxin beta Receptor / metabolism
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Mice
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Receptor, Notch2 / deficiency
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Receptor, Notch2 / metabolism*
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Receptors, Cell Surface / metabolism
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Signal Transduction
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Spleen / immunology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Wound Healing / genetics
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Wound Healing / immunology
Substances
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Antigens, CD
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CD11b Antigen
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DEC-205 receptor
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Interleukin-23
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Lectins, C-Type
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Ltbr protein, mouse
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Lymphotoxin beta Receptor
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Minor Histocompatibility Antigens
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Receptor, Notch2
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Receptors, Cell Surface
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Transcription Factors
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Zbtb46 protein, mouse