Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway.

• DOI: 10.1172/jci2406
• Publication Date: 2008-02-11T17:22:37Z
• Authors: A Ring; J N Weiser; E I Tuomanen
• Keywords: Transcytosis

Although Streptococcus pneumoniae is a major cause of meningitis in humans, the mechanisms underlying its traversal from circulation across blood-brain barrier (BBB) into subarachnoid space are poorly understood. One mechanism might involve transcytosis through microvascular endothelial cells. In this study we investigated ability pneumococci to invade and transmigrate monolayers rat human brain cells (BMEC). Significant variability was found invasive capacity clinical isolates. Phase variation transparent phenotype increased invasion as much 6-fold loss capsule approximately 200-fold. Invasion required choline pneumococcal cell wall, partially inhibited by antagonists platelet-activating factor (PAF) receptor on BMEC. Pneumococci that gained access an intracellular vesicle apical side monolayer subsequently were subject three fates. Most opaque variants killed. contrast, phase able transcytose basal surface BMEC manner dependent PAF presence choline-binding protein A. The remaining bacteria entering underwent previously unrecognized recycling surface. Transcytosis eventually becomes dominating process accounting for up 80% bacteria. Our data suggest interaction with results sorting so while non-PAF entry shunts exit reentry novel pathway.