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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 i...

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Detalles Bibliográficos
Autores principales: Satpathy, Ansuman T., Briseño, Carlos G., Lee, Jacob S., Ng, Dennis, Manieri, Nicholas A., KC, Wumesh, Wu, Xiaodi, Thomas, Stephanie R., Lee, Wan-Ling, Turkoz, Mustafa, McDonald, Keely G., Meredith, Matthew M., Song, Christina, Guidos, Cynthia J., Newberry, Rodney D., Ouyang, Wenjun, Murphy, Theresa L., Stappenbeck, Thaddeus S., Gommerman, Jennifer L., Nussenzweig, Michel C., Colonna, Marco, Kopan, Raphael, Murphy, Kenneth M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788683/
https://www.ncbi.nlm.nih.gov/pubmed/23913046
http://dx.doi.org/10.1038/ni.2679
Descripción
Sumario: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.