Intracellular parasitism by the human granulocytic ehrlichiosis bacterium through the P-selectin ligand, PSGL-1.
Human granulocytic ehrlichiosis (HGE) is a febrile tick-borne illness caused by a recently discovered intracellular bacterium remarkable for its tropism for professionally phagocytic neutrophils. Monoclonal antibodies against the P-selectin binding domain of the leukocyte P-selectin glycoprotein ligand, PSGL-1, prevented HGE cell binding and infection, as did enzymatic digestion of PSGL-1. Furthermore, simultaneous neoexpression in nonsusceptible cells of complementary DNAs for both PSGL-1 and its modifying alpha-(1,3) fucosyltransferase, Fuc-TVII, allowed binding and infection by HGE. Thus, the HGE bacterium specifically bound to fucosylated leukocyte PSGL-1. Selectin mimicry is likely central to the organism's unique ability to target and infect neutrophils.
Herron
M J
MJ
Division of Infectious Diseases, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Nelson
C M
CM
Larson
J
J
Snapp
K R
KR
Kansas
G S
GS
Goodman
J L
JL
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000382:microbiology; D002460:Cell Line; D004536:Ehrlichia / Q000378:metabolism / Q000472:pathogenicity*; D019084:Fluorescent Antibody Technique, Indirect; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006098:Granulocytes / Q000378:metabolism / Q000382:microbiology*; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D018716:Molecular Mimicry; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology*; D009844:Oligosaccharides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014162:Transfection
D000911:Antibodies, Monoclonal; D008024:Ligands; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; C084882:P-selectin ligand protein; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase