IAI Accepts, published online ahead of print on 29 June 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in ASM journals Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johns, J. L. Articles by Borjesson, D. L. Search for Related Content PubMed PubMed Citation Articles by Johns, J. L. Articles by Borjesson, D. L.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.00570-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Infection with Anaplasma phagocytophilum Induces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells

J. L. Johns, K. C. MacNamara, N. J. Walker, G. M. Winslow, and D. L. Borjesson^*

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA; Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA

^* To whom correspondence should be addressed. Email: dlborjesson{at}ucdavis.edu.

Infection with Anaplasma phagocytophilum, a gram-negative, LPS-negative, obligate intracellular bacteria, results in multiple peripheral blood cytopenias. We hypothesized that infection would result in decreased bone marrow (BM) function and shifts in hematopoietic progenitor cells (HPCs) and lineage-committed cells in a well-established murine model of infection. HPCs and lineage-committed progenitors were enumerated in BM and spleen during acute infection. BM cytokine production and BM CXCL12 expression were determined. Infection resulted in peripheral blood bicytopenia, marked decreases in the number of lineage-committed HPCs in the BM with concurrent increases in lineage-committed HPCs in the spleen and a mixed, predominantly myelosuppressive, BM cytokine environment. There was a significant downregulation of CXCL12 in BM cells that may be partially responsible for changes noted in HPC trafficking. Changes occurred in the absence of direct pathogen infection of BM cells. Hematopoietic lineage assessment demonstrated a loss of erythrocytes and B-lymphocytes from the BM with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on BM and spleen; however, peripheral blood neutrophil numbers appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Findings highlight a well-conserved series of events that we now demonstrate can be instigated by a LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.

This article has been cited by other articles:

• Schaff, U. Y., Trott, K. A., Chase, S., Tam, K., Johns, J. L., Carlyon, J. A., Genetos, D. C., Walker, N. J., Simon, S. I., Borjesson, D. L. (2010). Neutrophils exposed to A. phagocytophilum under shear stress fail to fully activate, polarize, and transmigrate across inflamed endothelium. Am. J. Physiol. Cell Physiol. 299: C87-C96 [Abstract] [Full Text]  
• MacNamara, K. C., Racine, R., Chatterjee, M., Borjesson, D., Winslow, G. M. (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 [Abstract] [Full Text]