title: Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro.
abstract: Previous experimental studies in a standard Transwell culture system have shown Streptococcus suis ability to compromise barrier function of porcine choroid plexus epithelial cells (PCPEC). The development of an 'inverted' Transwell filter system of PCPEC enables us now for the first time to investigate bacterial invasion and translocation from the physiologically relevant basolateral (blood) to the apical (cerebrospinal fluid) side. Most importantly, we observed specific invasion and translocation of S. suis across the PCPEC exclusively from the basolateral side. During this process, bacterial viability and the presence of a capsule as well as cytoskeletal regulation of PCPEC seemed to play an important role. No loss of barrier function was observed. Bacterial translocation could be significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002, but not by its inactive analogue Ly303511 or dexamethasone. Apotome imaging as well as electron microscopy revealed intracellular bacteria often in cell vacuoles. Thus, possibly regulated by the presence of a capsule, S. suis induces signals that depend on the lipid kinase phosphatidylinositol 3-kinase pathway, which paves the way for cellular uptake during the bacterial transcellular translocation process. Taken together, our data underline the relevance of the blood-cerebrospinal fluid barrier as a gate for bacterial entry into the central nervous system.
authors.affiliation: Pediatric Infectious Diseases, Department of Pediatrics, University Hospital Mannheim, Mannheim, Germany. tobias.tenenbaum@kikli.ma.uni-heidelberg.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Tenenbaum
authors.forename: Thalia
authors.initials: T
authors.lastname: Papandreou
authors.forename: Dorothee
authors.initials: D
authors.lastname: Gellrich
authors.forename: Ulrike
authors.initials: U
authors.lastname: Friedrichs
authors.forename: Annette
authors.initials: A
authors.lastname: Seibt
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Adam
authors.forename: Corinna
authors.initials: C
authors.lastname: Wewer
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
authors.forename: Christian
authors.initials: C
authors.lastname: Schwerk
authors.forename: Horst
authors.initials: H
authors.lastname: Schroten
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000382:microbiology*; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017011:Streptococcus suis / Q000502:physiology*; D013552:Swine; D014617:Vacuoles / Q000382:microbiology / Q000648:ultrastructure
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors