Anaplasma phagocytophilum infects cells of the megakaryocytic lineage through sialylated ligands but fails to alter platelet production

• Published in: Journal of medical microbiology Vol. 57; no. 4; pp. 416 - 423
• Main Authors: Granick, Jennifer L, Reneer, Dexter V, Carlyon, Jason A, Borjesson, Dori L
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.04.2008; Society for General Microbiology
• Subjects: Anaplasma phagocytophilum; Anaplasma phagocytophilum - metabolism; Anaplasma phagocytophilum - pathogenicity; Bacteriology; Biological and medical sciences; Blood Platelets - cytology; Cell Differentiation; Cell Line; Fundamental and applied biological sciences. Psychology; HL-60 Cells; Humans; Ligands; Megakaryocytes - microbiology; Membrane Glycoproteins - metabolism; Microbiology; Miscellaneous; Rickettsiales; Platelet; Anaplasmataceae; Bacteria; Cell lineage; Anaplasma; Infected cell
• ISSN: 0022-2615; 1473-5644
• DOI: 10.1099/jmm.0.47551-0

1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA 2 Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KT, USA 3 Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA 4 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, Davis, CA, USA Correspondence Dori L. Borjesson dlborjesson{at}ucdavis.edu Received 2 August 2007 Accepted 21 December 2007 Anaplasma phagocytophilum is an obligate intracellular bacterial pathogen that principally inhabits neutrophils. However, infection with A. phagocytophilum results in a moderate to marked thrombocytopenia. In host neutrophils, A. phagocytophilum uses sialylated ligands, primarily P-selectin glycoprotein ligand-1 (PSGL-1), to enter its host cell. PSGL-1 is expressed on a wide array of haematopoietic cells, including megakaryocytes. In this study, it was hypothesized that (i) cells of the megakaryocytic lineage (MEG-01 cells) would be susceptible to A. phagocytophilum infection and (ii) infection may induce alterations in platelet production contributing to infection-induced thrombocytopenia. It was found that MEG-01 cells are susceptible to infection. MEG-01 cells expressing abundant sialylated ligands were the most susceptible to infection, and the absence of sialylation, or blocking of PSGL-1, limited infection susceptibility. However, infected MEG-01 cells produced proplatelets and platelet-like particles comparable to uninfected cells. These results highlight a novel target of pathogen infection and suggest that the pathogen may utilize similar strategies to gain access to megakaryocytes. Direct pathogen modification of platelet production may not play a role in infection-induced thrombocytopenia. Abbreviations: FBS, fetal bovine serum; GA, granulocytic anaplasmosis; MK, megakaryocyte; p.i., post-infection; PLPs, platelet-like particles; PSGL-1, P-selectin glycoprotein-1; sLe x , sialyl Lewis x.