Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro.
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.
Tenenbaum
Tobias
T
Pediatric Infectious Diseases, Department of Pediatrics, University Hospital Mannheim, Mannheim, Germany. tobias.tenenbaum@kikli.ma.uni-heidelberg.de
Papandreou
Thalia
T
Gellrich
Dorothee
D
Friedrichs
Ulrike
U
Seibt
Annette
A
Adam
Rüdiger
R
Wewer
Corinna
C
Galla
Hans-Joachim
HJ
Schwerk
Christian
C
Schroten
Horst
H
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
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors