Satpathy AT, Briseno CG, Lee JS, Ng D, Manieri NA, Wu X, Thomas SR, KC W, Lee WL, Turkoz M, McDonald KG, Meredith MM, Guidos CJ, Newberry RD, Stappenbeck TS, Ouyang W, Murphy TL, Nussenzweig MC, Gommerman JL, Kopan R, Colonna M, Murphy KM.
Nature Immunology, 1 September 2013

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.