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Prepublished online as a Blood First Edition Paper on July 18, 2002; DOI 10.1182/blood-2002-03-0898.
Submitted March 21, 2002
Accepted July 2, 2002
Interaction of human hematopoietic stem cells with bacterial pathogens
Annette Kolb-Maurer*, Martin Wilhelm, Florian Weissinger, Eva-Bettina Brocker, and Werner Goebel
Department of Dermatology, University of Wuerzburg, Wuerzburg, Germany
Department of Internal medicine, University of Wuerzburg, Wuerzburg, Germany
Institute for Microbiology, University of Wuerzburg, Wuerzburg, Germany
* Corresponding author; email: ankolb{at}biozentrum.uni-wuerzburg.de.
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 comprised mainly of cells with the potential of differentiation in one or two 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 serovar 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.
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