title: Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling.
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.
  
  
  CONCLUSIONS
  Steady-state and emergency granulopoiesis are both dependent on TLR signaling.
authors.affiliation: Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Medical Center II, South West German Comprehensive Cancer Center, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bugl
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirths
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.forename: Maya C
authors.initials: MC
authors.lastname: André
authors.forename: Martin R
authors.initials: MR
authors.lastname: Müller
authors.forename: Elke
authors.initials: E
authors.lastname: Malenke
authors.forename: Tina
authors.initials: T
authors.lastname: Wiesner
authors.forename: Melanie
authors.initials: M
authors.lastname: Märklin
authors.forename: Julia-Stefanie
authors.initials: JS
authors.lastname: Frick
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kopp
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016179:Granulocyte Colony-Stimulating Factor; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse