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How Two Related Pathogens Commandeer Blood Cell Differentiation Print E-mail

 

Human monocytic ehrlichiosis (HME) is an emerging tick-borne disease caused by Ehrlichia chaffeensis. winslow-mcnamaraHME patients typically exhibit a severe loss of red blood cells and platelets. To investigate the cause of the blood cell loss, Gary M. Winslow of the Wadsworth Center, Albany, N.Y., and Dori Borjesson of the University of California, Davis, et al. infected mice with E. muris, a strain closely related to E. chaffeensis. As with human HME patients, the mice showed a loss of red blood cells and platelets. The team found that the capacity of bone marrow to manufacture myeloid cells was significantly lower than normal during infection. "Our studies suggest that dramatic changes in blood cell development and alterations in secondary lymphoid organ borjjohnsstructure may be underlying causes of hematological defects in HME patients," says Winslow. "In future experiments, we plan to address how bacterial infections affect the earliest blood cell progenitors, the hematopoietic stem cells. Changes in hematopoietic stem cell differentiation likely allow the body to generate particular blood cells needed to fight infection, as well as to restore normal bone marrow function once infections are resolved." As with Ehrlichia, Anaplasma phagocytophilum-apathogen that has the chutzpah to grow in neutrophils-rearranges differentiation in the bone marrow, according to the same two groups of researchers, led this time by Borjesson of U.C. Davis. "We have shown that after acute infection, the production of committed progenitor cells in the bone marrow shifts to favor granulocytes," says Borjesson. "There is a concurrent loss of B lymphocytes. In addition, erythroid cells are mobilized to the spleen. These changes may occur secondary to downregulation of the SDF-1/CXCR4 pathway. In addition, the cytokine profile in the bone marrow favors production of myelosuppressive cytokines, including the murine homologs of IL-8. These pathogen-induced changes in hematopoiesis may contribute to the decrease in blood cell number that characterizes infection with this bacterium." This work has relevance for clinical mobilization of stem cells for bone marrow transplant, and "the recognition that normal homeostatic mechanisms can be perturbed by inflammatory stimuli and infectious agents has important implications for patients needing cellular therapy. The identification of signals that subvert normal cell trafficking and promote persistent cytopenias or bone marrow failure is critical to assessment of risk factors associated with cell therapy."

(K. C. MacNamara, R. Racine, M. Chatterjee, D. L. Borjesson, and G. M. Winslow. 2009. Diminished hematopoietic activity associated with alterations in innate and adaptive immunity in a mouse model of human monocytic Ehrlichiosis. Infect. Immun. 77:4061-4069.)

J. L. Johns, K. C. MacNamara, N. J. Walker, G. M. Winslow, and D. L. Borjesson. 2009. Infection with Anaplasma phagocytophilum induces multilineage alterations in hematopoietic progenitor cells and peripheral blood cells. Infect. Immun. 77:4070-4080.)