title: Interaction of human hematopoietic stem cells with bacterial pathogens.
abstract: Primitive hematopoietic stem cells (HSCs) in the bone marrow are rare pluripotent cells with the capacity to give rise to all lineages of blood cells. During commitment, progenitor cells are composed mainly of cells with the potential for differentiation into 1 or 2 lineages. This commitment involves the acquisition of specific growth factor receptors and the loss of others. Viral and bacterial infections may lead to profound disturbance of hematopoiesis, which is possibly due to different susceptibility of HSCs to infectious agents. Here, we show that quiescent human HSCs are fully resistant to infection by the intracellular bacteria, Listeria monocytogenes and Salmonella enterica serovariation typhimurium, and the extracellular pathogen Yersinia enterocolitica. During myeloid/monocytic differentiation induced by incubation with stem cell factor, thrombopoietin, and flt-3 ligand, partially differentiated HSCs emerge, which readily take up these pathogens and also latex beads by macropinocytosis. After further monocytic differentiation, bacterial uptake by macropinocytosis still occurs but internalization of the pathogens is now mainly achieved by receptor-mediated phagocytosis. These results suggest that in the case of HSCs uptake mechanisms for bacteria develop sequentially.
authors.affiliation: Department of Dermatology, and Institute for Microbiology, Theodor-Boveri-Institute, University of Würzburg, Würzburg, Germany. ankolb@biozentrum.uni-wuerzburg.de
authors.forename: Annette
authors.initials: A
authors.lastname: Kolb-Mäurer
authors.forename: Martin
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Florian
authors.initials: F
authors.lastname: Weissinger
authors.forename: Eva-Bettina
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Werner
authors.initials: W
authors.lastname: Goebel
mesh_terms: D018952:Antigens, CD34; D001419:Bacteria / Q000472:pathogenicity*; D001424:Bacterial Infections; D002454:Cell Differentiation; D002470:Cell Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000166:cytology / Q000382:microbiology; D010587:Phagocytosis; D017452:Receptors, IgG
chemical_list: D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG