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.
ASJC Scopus subject areas
- Microbiology (medical)