title: Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens.
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.
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, Missouri, USA.
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Briseño
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Lee
authors.forename: Dennis
authors.initials: D
authors.lastname: Ng
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Manieri
authors.forename: Wumesh
authors.initials: W
authors.lastname: Kc
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thomas
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Lee
authors.forename: Mustafa
authors.initials: M
authors.lastname: Turkoz
authors.forename: Keely G
authors.initials: KG
authors.lastname: McDonald
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Meredith
authors.forename: Christina
authors.initials: C
authors.lastname: Song
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Guidos
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Raphael
authors.initials: R
authors.lastname: Kopan
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D037181:Lectins, C-Type / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D051883:Receptor, Notch2 / Q000172:deficiency / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; C093569:DEC-205 receptor; D053759:Interleukin-23; D037181:Lectins, C-Type; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D015778:Minor Histocompatibility Antigens; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C574226:Zbtb46 protein, mouse
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