Strain-dependent disruption of blood–cerebrospinal fluid barrier byStreptoccocus suisin vitro

Abstract

Streptococcus suis capsular type 2 is an important agent of diseases including meningitis among pigs worldwide, and is also a zoonotic agent. The barrier function of the choroid plexus epithelium that constitutes the structural basis for the blood-cerebrospinal fluid (CSF) barrier has not been elucidated yet in bacterial meningitis. We investigated the influence of various S. suis isolates on the barrier function of cultured porcine choroid plexus epithelial cells with respect to the transepithelial resistance and paracellular [(3)H]-mannitol flux. Preferentially apical application of S. suis isolates significantly decreased transepithelial resistance and significantly increased paracellular [(3)H]-mannitol flux in a time-, dose- and strain-dependent manner. Viable S. suis isolates caused cytotoxicity determined by lactate dehydrogenase assay and electron microscopy, whereas S. suis sonicates and UV-inactivated S. suis did not cause cytotoxicity. The observed effects on porcine choroid plexus epithelial cells barrier function could not exclusively be ascribed to known virulence factors of S. suis such as suilysin. In conclusion, S. suis isolates induce loss of blood-cerebrospinal fluid barrier function in an in vitro model. Thus, S. suis may facilitate trafficking of bacteria and leucocytes across the blood-cerebrospinal fluid barrier. The underlying mechanisms for the barrier breakdown have yet to be determined.

Use of Selective Capture of Transcribed Sequences To Identify Genes Preferentially Expressed byStreptococcus suisupon Interaction with Porcine Brain Microvascular Endothelial Cells

“…suis needs to attain the central nervous system (CNS) in order to cause meningitis in swine. It has been suggested that this pathogen might reach the CNS by crossing the porcine blood-brain barrier (BBB) by transcytosis through porcine brain microvascular endothelial cells (PBMEC) and/or porcine choroid plexus epithelial cells, as well as by disruption of the barrier caused by toxic effects on BBB-forming cells (11,36). Support for these mechanisms has been provided by recent studies showing that S. suis is able to affect the viability of porcine choroid plexus epithelial cells through necrotic and apoptotic mechanisms (37) and to adhere to and invade in vitro-cultured PBMEC (38).…”

Isolation and characterization of α-enolase, a novel fibronectin-binding protein from Streptococcus suis

“…Once in the bloodstream, S. suis resists phagocytosis and killing by neutrophils and monocytes (Chabot-Roy et al, 2006;Charland et al, 1998;Segura et al, 1998;Smith et al, 1999). In the event that S. suis fails to cause acute fatal septicaemia, bacteria are able to reach the CNS via different mechanisms that are only partially elucidated, such as adhesion to, with or without toxicity, and invasion of brain microvascular endothelial cells (BMEC) (Benga et al, 2005;Charland et al, 2000;Vanier et al, 2004) and/or choroid plexus epithelial cells (Tenenbaum et al, 2005(Tenenbaum et al, , 2006. In fact, interactions of S. suis with both fibronectin and plasminogen may play a role in some of these mechanisms.…”

Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis

“…Suilysin is known to affect porcine choroid plexus epithelial cells (40), and cytotoxic effects of suilysin have also been reported for brain microvascular endothelial cells (41,42). Furthermore, suilysin-stimulated release of proinflammatory molecules, such as arachidonic acid (43) and interleukin-8 (44,45), may play an important role in initiating changes in permeability and adhesion properties of the blood brain and the blood cerebrospinal fluid barriers, promoting immune cells to enter the central nervous system.…”