Anaplasma phagocytophilum infects cells of the megakaryocytic lineage through sialylated ligands but fails to alter platelet production.
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.
Granick
Jennifer L
JL
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
Reneer
Dexter V
DV
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KT, USA.
Carlyon
Jason A
JA
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Borjesson
Dori L
DL
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, Davis, CA, USA.
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*
D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein