Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection.
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.
Thomas
Venetta
V
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. venetta.thomas@yale.edu
Fikrig
Erol
E
D041081:Anaplasma phagocytophilum / Q000378:metabolism / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D018922:HL-60 Cells / Q000382:microbiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000382:microbiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D017346:Protein Serine-Threonine Kinases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases