Abstract
Anaplasma phagocytophilum, an obligate intracellular pathogen that persists within polymorphonuclear leucocytes, is the second most common tick-borne agent in North America. We now show that infection of a promyelocytic cell line and neutrophils with A. phagocytophilum results in pathogen-specific tyrosine phosphorylation of ROCK1. Phosphorylation is associated with PSGL-1 and Syk, because PSGL-1 blocking antibodies and siRNA targeting Syk interfere with ROCK1 phosphorylation in A. phagocytophilum-infected cells. Knockdown of either Syk or ROCK1 also markedly impaired A. phagocytophilum infection. These data demonstrate a role for A. phagocytophilum-mediated ROCK1 phosphorylation in infection, and suggests that inhibiting this pathway may lead to new, non-antibiotic strategies to treat human granulocytic anaplasmosis.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anaplasma phagocytophilum / metabolism
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Anaplasma phagocytophilum / pathogenicity*
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Gene Expression Regulation
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HL-60 Cells / microbiology
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Neutrophils / microbiology
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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RNA Interference
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Syk Kinase
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Tyrosine / metabolism*
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rho-Associated Kinases
Substances
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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P-selectin ligand protein
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Tyrosine
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Protein Serine-Threonine Kinases
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ROCK1 protein, human
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rho-Associated Kinases