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Prepublished online as a Blood First Edition Paper on July 18, 2002; DOI 10.1182/blood-2002-03-0898.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3703-3709
IMMUNOBIOLOGY
Interaction of human hematopoietic stem cells with
bacterial pathogens
Annette Kolb-Mäurer,
Martin Wilhelm,
Florian Weissinger,
Eva-Bettina Bröcker, and
Werner Goebel
From the Departments of Dermatology and Internal
Medicine, and Institute for Microbiology, Theodor-Boveri-Institute,
University of Würzburg, Würzburg, Germany.
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.
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