Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

被引：183

作者：

Askenase, Michael H. ^{[1
,2
]}

Han, Seong-Ji ^{[1
]}

Byrd, Allyson L. ^{[1
,3
]}

da Fonseca, Denise Morais ^{[1
]}

Bouladoux, Nicolas ^{[1
]}

Wilhelm, Christoph ^{[1
]}

Konkel, Joanne E. ^{[4
,5
]}

Hand, Timothy W. ^{[1
]}

Lacerda-Queiroz, Norinne

Su, Xin-zhuan ^{[6
]}

Trinchieri, Giorgio ^{[7
]}

Grainger, John R. ^{[1
,4
,5
]}

Belkaid, Yasmine ^{[1
]}

机构：

[1] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA

[2] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA

[3] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA

[4] Univ Manchester, MCCIR, Manchester M13 9NT, Lancs, England

[5] Univ Manchester, Fac Life Sci, Manchester M13 9NT, Lancs, England

[6] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA

[7] NCI, Expt Immunol Lab, Head Canc & Inflammat Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA

来源：

IMMUNITY | 2015年 / 42卷 / 06期

基金：

英国惠康基金;

关键词：

CD8-ALPHA(+) DENDRITIC CELLS; INFLAMMATORY MONOCYTES; TOXOPLASMA-GONDII; T-CELLS; MACROPHAGES; HOMEOSTASIS; GAMMA; DIFFERENTIATION; PROGENITOR; RESISTANCE;

D O I：

10.1016/j.immuni.2015.05.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tissue-infiltrating Ly6C(hi) monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-gamma promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DCs) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals after tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.

引用

页码：1130 / 1142

页数：13

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