<p>In the central nervous system (CNS), the highly vascularized choroid plexus (CP) produces the cerebrospinal fluid (CSF) and also acts as a blood-CSF barrier (BCSFB). Due to its location in the ventricular system of the brain, the CP can be used by pathogens such as bacteria to enter the CNS by crossing from the blood into the brain. This process, which can lead to meningitis, encephalitis and meningoencephalitis, is usually prevented by the BCSFB. Since barrier function is thought to be mainly executed by the CP epithelium, whose cells are connected to each other by dense tight junction (TJ) strands, in vitro studies of bacterial pathogens interacting with the BCSFB have routinely been performed using CP epithelial cells only. Recent data have shown that the CP endothelium can also contribute to barrier function at the BCSFB. Here, we used immortalized human CP endothelial cells (iHCPEnC) to investigate the interaction of the CP endothelium with the bacterial pathogen <i>Listeria monocytogenes</i> (<i>Lm</i>). Although <i>Lm</i> adhere to iHCPEnC, the endothelial cells are only weakly invaded by <i>Lm</i>, but readily transmigrated, in contrast to a CP epithelial cell line (HIBCPP cells). In a two-cell type model of the CP <i>Lm</i> transmigrated across iHCPEnC and invaded into HIBCPP cells, indicating that the CP endothelium does not pose a particularly strong barrier to <i>Lm</i> when attempting to overcome the BCSFB. Epithelial invasion was reduced compared to a model consisting of only HIBCPP cells, suggesting a regulatory impact of the CP endothelium.</p>

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Interaction of Listeria monocytogenes with the human choroid plexus endothelium in vitro: impact on invasion of the epithelium

  • Carolin Stump-Guthier,
  • Sandrin Schulze,
  • Walter Muranyi,
  • Mobarak Abu Mraheil,
  • Torsten Hain,
  • Michael Hagmann,
  • Hiroshi Ishikawa,
  • Horst Schroten,
  • Christian Schwerk,
  • Stefan Weichert

摘要

In the central nervous system (CNS), the highly vascularized choroid plexus (CP) produces the cerebrospinal fluid (CSF) and also acts as a blood-CSF barrier (BCSFB). Due to its location in the ventricular system of the brain, the CP can be used by pathogens such as bacteria to enter the CNS by crossing from the blood into the brain. This process, which can lead to meningitis, encephalitis and meningoencephalitis, is usually prevented by the BCSFB. Since barrier function is thought to be mainly executed by the CP epithelium, whose cells are connected to each other by dense tight junction (TJ) strands, in vitro studies of bacterial pathogens interacting with the BCSFB have routinely been performed using CP epithelial cells only. Recent data have shown that the CP endothelium can also contribute to barrier function at the BCSFB. Here, we used immortalized human CP endothelial cells (iHCPEnC) to investigate the interaction of the CP endothelium with the bacterial pathogen Listeria monocytogenes (Lm). Although Lm adhere to iHCPEnC, the endothelial cells are only weakly invaded by Lm, but readily transmigrated, in contrast to a CP epithelial cell line (HIBCPP cells). In a two-cell type model of the CP Lm transmigrated across iHCPEnC and invaded into HIBCPP cells, indicating that the CP endothelium does not pose a particularly strong barrier to Lm when attempting to overcome the BCSFB. Epithelial invasion was reduced compared to a model consisting of only HIBCPP cells, suggesting a regulatory impact of the CP endothelium.