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

被引：356

作者：

Satpathy, Ansuman T. ^{[1
]}

Briseno, Carlos G. ^{[1
]}

Lee, Jacob S. ^{[1
]}

Ng, Dennis ^{[2
]}

Manieri, Nicholas A. ^{[1
]}

Wumesh, K. C. ^{[1
]}

Wu, Xiaodi ^{[1
]}

Thomas, Stephanie R. ^{[1
]}

Lee, Wan-Ling ^{[1
]}

Turkoz, Mustafa ^{[3
]}

McDonald, Keely G. ^{[4
]}

Meredith, Matthew M. ^{[5
]}

Song, Christina ^{[1
]}

Guidos, Cynthia J. ^{[2
,6
]}

Newberry, Rodney D. ^{[4
]}

Ouyang, Wenjun ^{[7
]}

Murphy, Theresa L. ^{[1
]}

Stappenbeck, Thaddeus S. ^{[1
]}

Gommerman, Jennifer L. ^{[2
]}

Nussenzweig, Michel C. ^{[5
,8
]}

Colonna, Marco ^{[1
]}

Kopan, Raphael ^{[3
]}

Murphy, Kenneth M. ^{[1
,9
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA

[2] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA

[4] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA

[5] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA

[6] Hosp Sick Children, Res Inst, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada

[7] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA

[8] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

[9] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 09期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

INNATE LYMPHOID-CELLS; ROR-GAMMA-T; LY6C(HI) MONOCYTES; SIGNALING CONTROLS; STEM-CELLS; DIFFERENTIATION; MIGRATION; HOMEOSTASIS; EXPRESSION; INFECTION;

D O I：

10.1038/ni.2679

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：937 / +

页数：15

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