Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1642-1651
Leishmania donovani infection of bone marrow stromal
macrophages selectively enhances myelopoiesis, by a mechanism involving
GM-CSF and TNF-
Sara E. J. Cotterell,
Christian R. Engwerda, and
Paul M. Kaye
Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London, UK.
Alterations in hematopoiesis are common in experimental infectious
disease. However, few studies have addressed the mechanisms underlying
changes in hematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. In experimental visceral leishmaniasis, caused by infection with the
protozoan parasite Leishmania donovani, parasites persist in
the spleen and bone marrow, and their expansion in these sites is
associated with increases in local hematopoietic activity. The results
of this study show that L donovani targets bone
marrow stromal macrophages in vivo and can infect and multiply in
stromal cell lines of macrophage, but not other lineages in vitro.
Infection of stromal macrophages increases their capacity to support
myelopoiesis in vitro, an effect mediated mainly through the induction
of granulocyte macrophage-colony stimulating factor and tumor necrosis
factor-
. These data are the first to directly demonstrate that
intracellular parasitism of a stromal cell population may modify its
capacity to regulate hematopoiesis during infectious disease.
