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Infection and Immunity, September 2009, p. 4061-4069, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.01550-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Diminished Hematopoietic Activity Associated with Alterations in Innate and Adaptive Immunity in a Mouse Model of Human Monocytic Ehrlichiosis

Katherine C. MacNamara,¹ Rachael Racine,¹ Madhumouli Chatterjee,¹ Dori Borjesson,² and Gary M. Winslow^1*

Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, New York 12201-2002,¹ Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, California²

Received 22 December 2008/ Returned for modification 23 January 2009/ Accepted 6 May 2009

Human monocytic ehrlichiosis (HME) is a tick-borne disease caused by Ehrlichia chaffeensis. Patients exhibit diagnostically important hematological changes, including anemia and thrombocytopenia, although the basis of the abnormalities is unknown. To begin to understand these changes, we used a mouse model of ehrlichiosis to determine whether the observed hematological changes induced by infection are associated with altered hematopoietic activity. Infection with Ehrlichia muris, a pathogen closely related to E. chaffeensis, resulted in anemia, thrombocytopenia, and a marked reduction in bone marrow cellularity. CFU assays, conducted on days 10 and 15 postinfection, revealed a striking decrease in multipotential myeloid and erythroid progenitors. These changes were accompanied by an increase in the frequency of immature granulocytes in the bone marrow and a decrease in the frequency of B lymphocytes. Equally striking changes were observed in spleen cellularity and architecture, and infected mice exhibited extensive extramedullary hematopoiesis. Splenomegaly, a characteristic feature of E. muris infection, was associated with an expanded and disorganized marginal zone and a nearly 66-fold increase in the level of Ter119⁺ erythroid cells, indicative of splenic erythropoiesis. We hypothesize that inflammation associated with ehrlichia infection suppresses bone marrow function, induces the emigration of B cells, and establishes hematopoietic activity in the spleen. We propose that these changes, which may be essential for providing the innate and acquired immune cells to fight infection, are also responsible in part for blood cytopenias and other clinical features of HME.

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* Corresponding author. Mailing address: Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, NY 12201-2002. Phone: (518) 473-2795. Fax: (518) 486-9858. E-mail: gary.winslow{at}wadsworth.org

Published ahead of print on 18 May 2009.

Editor: B. A. McCormick

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Infection and Immunity, September 2009, p. 4061-4069, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.01550-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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