Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling

被引：78

作者：

Bugl, Stefanie ^{[1
]}

Wirths, Stefan ^{[1
]}

Radsak, Markus P. ^{[2
]}

Schild, Hansjoerg ^{[3
]}

Stein, Pamela ^{[3
]}

Andre, Maya C. ^{[4
]}

Mueller, Martin R. ^{[1
]}

Malenke, Elke ^{[1
]}

Wiesner, Tina ^{[1
]}

Maerklin, Melanie ^{[1
]}

Frick, Julia-Stefanie ^{[5
]}

Handgretinger, Rupert ^{[3
]}

Rammensee, Hans-Georg ^{[6
]}

Kanz, Lothar ^{[1
]}

Kopp, Hans-Georg ^{[1
]}

机构：

[1] Univ Hosp Tuebingen, SW German Comprehens Canc Ctr, Dept Med Oncol Hematol Immunol Rheumatol & Pulmon, Med Ctr 2, Tubingen, Germany

[2] Johannes Gutenberg Univ Mainz, Med Ctr, Dept Internal Med Hematol Oncol Pneumol 3, D-55122 Mainz, Germany

[3] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Immunol, D-55122 Mainz, Germany

[4] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, Tubingen, Germany

[5] Univ Tubingen, Inst Med Microbiol & Hyg, Tubingen, Germany

[6] Univ Tubingen, Inst Cell Biol, Dept Immunol, Tubingen, Germany

来源：

BLOOD | 2013年 / 121卷 / 05期

关键词：

COLONY-STIMULATING FACTOR; TOLL-LIKE RECEPTORS; STEM-CELL MOBILIZATION; BONE-MARROW; G-CSF; ADAPTIVE IMMUNITY; MICE; GRANULOCYTE; INNATE; GRANULOPOIESIS;

D O I：

10.1182/blood-2012-05-429589

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Polymorphonuclear neutrophil granulocytes (neutrophils) are tightly controlled by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Although it has long been known that marrow cellularity is inversely correlated with G-CSF levels, the mechanism linking peripheral clearance to production remains unknown. Herein, the feedback response to antibody induced neutropenia is characterized to consist of G-CSF-dependent shifts of marrow hematopoietic progenitor populations including expansion of the lin(-)/Sca-1(+)/c-kit(+) (LSK) and granulocyte macrophage progenitor (GMP) compartments at the expense of thrombopoietic and red cell precursors. Evidence is provided that positive feedback regulation is independent from commensal germs as well as T, B, and NK cells. However, in vivo feedback is impaired in TLR4(-/-) and TRIF-/-, but not MyD88(-/-) animals. In conclusion, steady-state neutrophil homeostasis is G-CSF-dependent and regulated through pattern-recognition receptors, thereby directly linking TLR-triggering to granulopoiesis. (Blood. 2013;121(5):723-733)

引用

页码：723 / 733

页数：11

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[1] A clonogenic common myeloid progenitor that gives rise to all myeloid lineages [J].