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

Ansuman T. Satpathy, Carlos G. Briseño, Jacob S. Lee, Dennis Ng, Nicholas A. Manieri, Wumesh Kc, Xiaodi Wu, Stephanie R. Thomas, Wan Ling Lee, Mustafa Turkoz, Keely G. McDonald, Matthew M. Meredith, Christina Song, Cynthia J. Guidos, Rodney D. Newberry, Wenjun Ouyang, Theresa L. Murphy, Thaddeus S. Stappenbeck, Jennifer L. Gommerman, Michel C. NussenzweigMarco Colonna, Raphael Kopan, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

324 Scopus citations


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.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalNature immunology
Issue number9
StatePublished - Sep 2013


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