title: Polar invasion and translocation of Neisseria meningitidis and Streptococcus suis in a novel human model of the blood-cerebrospinal fluid barrier.
abstract: Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.
authors.affiliation: Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. christian.schwerk@medma.uni-heidelberg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Schwerk
authors.forename: Thalia
authors.initials: T
authors.lastname: Papandreou
authors.forename: Daniel
authors.initials: D
authors.lastname: Schuhmann
authors.forename: Laura
authors.initials: L
authors.lastname: Nickol
authors.forename: Julia
authors.initials: J
authors.lastname: Borkowski
authors.forename: Ulrike
authors.initials: U
authors.lastname: Steinmann
authors.forename: Natascha
authors.initials: N
authors.lastname: Quednau
authors.forename: Carolin
authors.initials: C
authors.lastname: Stump
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Tobias
authors.initials: T
authors.lastname: Tenenbaum
authors.forename: Horst
authors.initials: H
authors.lastname: Schroten
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002555:Cerebrospinal Fluid / Q000382:microbiology*; D002831:Choroid Plexus / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D017097:Electric Impedance; D004848:Epithelium / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007444:Inulin / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009068:Movement; D009345:Neisseria meningitidis / Q000166:cytology / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D010212:Papilloma / Q000382:microbiology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017011:Streptococcus suis / Q000166:cytology / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; D007444:Inulin; D016650:Fluorescein-5-isothiocyanate