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Updated: May 16, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling
Stefanie Bugl1, Stefan Wirths, Markus P Radsak
1Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Medical Center II, South West German Comprehensive Cancer Center, University Hospital of Tuebingen, Tuebingen, Germany.
Unlabelled:
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.
Key Points:
Steady-state and emergency granulopoiesis are both dependent on TLR signaling.
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