title: Anaplasma phagocytophilum infects cells of the megakaryocytic lineage through sialylated ligands but fails to alter platelet production.
abstract: 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.
authors: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors: Jennifer L
authors: JL
authors: Granick
authors: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KT, USA.
authors: Dexter V
authors: DV
authors: Reneer
authors: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
authors: Jason A
authors: JA
authors: Carlyon
authors: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, Davis, CA, USA.
authors: Dori L
authors: DL
authors: Borjesson
mesh_terms: D041081:Anaplasma phagocytophilum / Q000378:metabolism / Q000472:pathogenicity*; D001792:Blood Platelets / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D008533:Megakaryocytes / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein