title: Acanthamoeba interactions with the blood-brain barrier under dynamic fluid flow.
abstract: Acanthamoeba granulomatous encephalitis (AGE), caused by Acanthamoeba castellanii, is a fatal infection of immunocompromised individuals. The pathogenesis of blood-brain barrier (BBB) breach remains unknown. Using a novel in vitro BBB infection model under flow conditions, demonstrates that increases in flow rates lead to decreased binding of A. castellanii to host cells. This is a distinct departure from previous findings under static conditions. However, similarly to static conditions binding of A. castellanii to host cells is host mannose dependent. Disruption of the host cell monolayer was independent of amoeba binding, but dependent on secreted serine proteases. For the first time we report the binding dynamics of A. castellanii under physiological conditions, showing that BBB disruption is not directly linked to binding, instead it is reliant on secreted proteases. Our results offer a platform on which therapies designed at modulating physiological parameters can improve the outcome of infection with A. castellanii.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: James
authors.initials: J
authors.lastname: Edwards-Smallbone
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pleass
authors.forename: Naveed A
authors.initials: NA
authors.lastname: Khan
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Flynn
mesh_terms: D048248:Acanthamoeba castellanii / Q000502:physiology*; D000562:Amebiasis / Q000469:parasitology*; D001812:Blood-Brain Barrier / Q000469:parasitology*; D001921:Brain / Q000166:cytology / Q000469:parasitology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004660:Encephalitis / Q000469:parasitology*; D042783:Endothelial Cells / Q000469:parasitology; D004730:Endothelium, Vascular / Q000166:cytology / Q000469:parasitology; D006801:Humans; D057446:Hydrodynamics; D037601:Mannose-Binding Lectin / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism / Q000469:parasitology; D057057:Serine Proteases / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D037601:Mannose-Binding Lectin; D057057:Serine Proteases