title: Divergent interactions of Ehrlichia chaffeensis- and Anaplasma phagocytophilum-infected leukocytes with endothelial cell barriers.
abstract: Human anaplasmosis (formerly human granulocytic ehrlichiosis) and human monocytic ehrlichiosis (HME) are emerging tick-borne infections caused by obligate intracellular bacteria in the family Anaplasmataceae. Clinical findings include fever, headache, myalgia, leukopenia, thrombocytopenia, and hepatic inflammatory injury. Whereas Ehrlichia chaffeensis (HME) often causes meningoencephalitis, this is rare with Anaplasma phagocytophilum infection. The abilities of infected primary host monocytes and neutrophils and of infected HL-60 cells to cross human umbilical vein endothelial cell-derived EA.hy926 cell barriers and human brain microvascular cells (BMEC), a human blood-brain barrier model, were studied. Uninfected monocyte/macrophages crossed endothelial cell barriers six times more efficiently than neutrophils. More E. chaffeensis-infected monocytes transmigrated than uninfected monocytes, whereas A. phagocytophilum suppressed neutrophil transmigration. Differences were not due to barrier dysfunction, as transendothelial cell resistivities were the same for uninfected cell controls. Similar results were obtained for HL-60 cells used as hosts for E. chaffeensis and A. phagocytophilum. Differential transmigration of E. chaffeensis- and A. phagocytophilum-infected leukocytes and HL-60 cells confirmed a role for the pathogen in modifying cell migratory capacity. These results support the hypothesis that Anaplasmataceae intracellular infections lead to unique pathogen-specific host cell functional alterations that are likely important for pathogen survival, pathogenesis, and disease induction.
authors.affiliation: Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.forename: Kyoung-Seong
authors.initials: KS
authors.lastname: Choi
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Grab
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Dumler
mesh_terms: D041081:Anaplasma phagocytophilum / Q000472:pathogenicity*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D002461:Cell Line, Transformed; D002465:Cell Movement; D018469:Ehrlichia chaffeensis / Q000472:pathogenicity*; D016873:Ehrlichiosis / Q000276:immunology / Q000382:microbiology; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000382:microbiology*; D008833:Microcirculation; D014471:Umbilical Veins