title: Toxoplasma gondii tachyzoites cross retinal endothelium assisted by intercellular adhesion molecule-1 in vitro.
abstract: Retinal infection is the most common clinical manifestation of toxoplasmosis. The route by which circulating Toxoplasma gondii tachyzoites cross the vascular endothelium to enter the human retina is unknown. Convincing studies using murine encephalitis models have strongly implicated leukocyte taxis as one pathway used by the parasite to access target organs. To establish whether tachyzoites might also interact directly with vascular endothelium, we populated a transwell system with human ocular endothelial cells. Human retinal endothelial monolayers permitted transmigration of tachyzoites of RH and three natural isolate strains. Antibody blockade of intercellular adhesion molecule-1 significantly reduced this migration, but did not impact tachyzoite movement across an endothelial monolayer derived from the choroid, which lies adjacent to the retina within the eye. In demonstrating that tachyzoites are capable of independent migration across human vascular endothelium in vitro, this study carries implications for the development of therapeutics aimed at preventing access of T. gondii to the retina.
authors.affiliation: Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: João M
authors.initials: JM
authors.lastname: Furtado
authors.forename: Arpita S
authors.initials: AS
authors.lastname: Bharadwaj
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Chipps
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Pan
authors.forename: Liam M
authors.initials: LM
authors.lastname: Ashander
authors.forename: Justine R
authors.initials: JR
authors.lastname: Smith
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply / Q000166:cytology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism; D009068:Movement / Q000187:drug effects; D012171:Retinal Vessels / Q000166:cytology; D013045:Species Specificity; D014122:Toxoplasma / Q000145:classification / Q000276:immunology* / Q000502:physiology; D014126:Toxoplasmosis, Ocular / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
chemical_list: D000906:Antibodies; D018799:Intercellular Adhesion Molecule-1