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Infection and Immunity, September 2009, p. 4018-4027, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00527-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Anaplasma phagocytophilum Dense-Cored Organisms Mediate Cellular Adherence through Recognition of Human P-Selectin Glycoprotein Ligand 1{triangledown}

Matthew J. Troese and Jason A. Carlyon*

Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia

Received 12 May 2009/ Returned for modification 8 June 2009/ Accepted 7 July 2009

Anaplasma phagocytophilum is an obligate intracellular bacterium that infects granulocytes to cause human granulocytic anaplasmosis. The susceptibilities of human neutrophils and promyelocytic HL-60 cells to A. phagocytophilum are linked to bacterial usage of P-selectin glycoprotein ligand 1 (PSGL-1) as a receptor for adhesion and entry. A. phagocytophilum undergoes a biphasic developmental cycle, transitioning between a smaller electron dense-cored cell (DC), which has a dense nucleoid, and a larger, pleomorphic electron lucent reticulate cell (RC), which has a dispersed nucleoid. The pathobiological roles of each form have not been elucidated. To ascertain the role of each form, we used electron microscopy to monitor bacterial binding, entry, and intracellular development within HL-60 cells. Only DCs were observed binding to and inducing uptake by HL-60 cells. By 12 h, internalized DCs had transitioned to RCs, which had initiated replication. By 24 h, large RC numbers were observed within individual inclusions. Reinfection had occurred by 36 h, as individual, vacuole-enclosed DCs and RCs were again observed. The abilities of DC- and RC-enriched A. phagocytophilum populations to bind and/or infect HL-60 cells or Chinese hamster ovary cells transfected to express PSGL-1 (PSGL-1 CHO) were compared. Only DCs bound PSGL-1 CHO cells and did so in a PSGL-1-blocking antibody-inhibitable manner. These results demonstrate that the respective roles of A. phagocytophilum DCs and RCs are consistent with analogous forms of other obligate intracellular pathogens that undergo biphasic development and hint that the PSGL-1-targeting adhesin(s) may be upregulated or optimally posttranslationally modified on DCs.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Molecular Medicine Research Building, 1220 East Broad Street, Room 4052, P.O. Box 980678, Richmond, VA 23298-0678. Phone: (804) 628-3382. Fax: (804) 828-9946. E-mail: jacarlyon{at}vcu.edu

{triangledown} Published ahead of print on 13 July 2009.

Editor: R. P. Morrison

Infection and Immunity, September 2009, p. 4018-4027, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00527-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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