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

Defense against attaching and effacing (A/E) bacteria requires the sequential generation of interleukin 23 (IL-23) and IL-22 to induce protective mucosal responses. While 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 specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the A/E pathogen Citrobacter rodentium. We found that Notch2 controlled the terminal stage of cDC differentiation. Notch2-dependent intestinal CD11b(+) cDCs, but not Batf3-dependent CD103(+) cDCs, were an obligate source of IL-23 required to survive C. rodentium infection. These results provide the first demonstration of a non-redundant function of CD11b(+) cDCs in response to pathogens in vivo.