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

S Bugl, S Wirths, MP Radsak, H Schild… - Blood, The Journal …, 2013 - ashpublications.org
S Bugl, S Wirths, MP Radsak, H Schild, P Stein, MC André, MR Müller, E Malenke…
Blood, The Journal of the American Society of Hematology, 2013ashpublications.org
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 …
Abstract
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.
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