Leishmania donovani infection of bone marrow stromal macrophages selectively enhances myelopoiesis, by a mechanism involving GM-CSF and TNF-alpha

Alterations in hematopoiesis are common in experimental infectious disease. However, few studies have addressed the mechanisms underlying changes in h ematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. In experimental visceral leishman iasis, caused by infection with the protozoan parasite Leishmania donovani, parasites persist in the spleen and bone marrow, and their expansion in th ese sites is associated with increases in local hematopoietic activity. The results of this study show that L donovani targets bone marrow stromal mac rophages in vivo and can infect and multiply in stromal cell lines of macro phage, but not other lineages in vitro. Infection of stromal macrophages in creases their capacity to support myelopoiesis in vitro, an effect mediated mainly through the induction of granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha. These data are the first to directl y demonstrate that intracellular parasitism of a stromal cell population ma y modify its capacity to regulate hematopoiesis during infectious disease. (C) 2000 by The American Society of Hematology.