title: Sensing and translation of pathogen signals into demand-adapted myelopoiesis.
abstract: OBJECTIVE
  During severe systemic infection, steady-state hematopoiesis is switched to demand-adapted myelopoiesis, leading to increased myeloid progenitor proliferation and, depending on the context and type of pathogen, enhanced granulocytic or monocytic differentiation, respectively. We will review the recent advances in understanding direct and indirect mechanisms by which different pathogen signals are detected and subsequently translated into demand-adapted myelopoiesis.
  
  
  RESULTS
  Enhanced myeloid progenitor proliferation and neutrophil differentiation following infection with prototypic Gram-negative bacterium Escherichia coli is mediated by granulocyte colony-stimulating factor, and reactive oxygen species released from endothelial cells and mature myeloid cells, respectively. Furthermore, hematopoietic stem and progenitor cells directly sense pathogen signals via Toll-like receptors and contribute to emergency granulopoiesis via release and subsequent autocrine and paracrine action of myelopoietic cytokines including IL-6. Moreover, emergency monocytopoiesis upon viral infection depends on T cell-derived IFNγ and release of IL-6 from bone marrow stromal cells.
  
  
  CONCLUSIONS
  A complex picture is evolving in which various hematopoietic and nonhematopoietic cell types interact with the hematopoietic system in an intricate manner to shape an appropriate hematopoietic response to specific infectious stimuli.
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Boettcher
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D059630:Mesenchymal Stem Cells; D038042:Myelopoiesis / Q000502:physiology*; D015398:Signal Transduction