title: Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells.
abstract: Systemic bacterial infection is rapidly recognized as an emergency state leading to neutrophil release into the circulation and increased myeloid cell production within the bone marrow. However, the mechanisms of sensing infection and subsequent translation into emergency myelopoiesis have not been defined. In this study, we demonstrate in vivo in mice that, surprisingly, selective TLR4 expression within the hematopoietic compartment fails to induce LPS-driven emergency myelopoiesis. In contrast, TLR4-expressing nonhematopoietic cells are indispensable for LPS-induced, G-CSF-mediated myelopoietic responses. Furthermore, LPS-induced emergency myelopoiesis is independent of intact IL-1RI signaling and, thus, does not require inflammasome activation. Collectively, our findings reveal a key and nonredundant role for nonhematopoietic compartment pathogen sensing that is subsequently translated into cytokine release for enhanced, demand-adapted myeloid cell production.
authors.affiliation: Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Boettcher
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schmid
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takizawa
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D038042:Myelopoiesis / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4