RGD Reference Report - Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. - Rat Genome Database

RGD Reference Report - Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway. - Rat Genome Database

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Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway.
Authors:	Ring, A Weiser, JN Tuomanen, EI
Citation:	Ring A, etal., J Clin Invest. 1998 Jul 15;102(2):347-60.
RGD ID:	10041053
Pubmed:	PMID:9664076 (View Abstract at PubMed)
PMCID:	PMC508893 (View Article at PubMed Central)
DOI:	DOI:10.1172/JCI2406 (Journal Full-text)
Although Streptococcus pneumoniae is a major cause of meningitis in humans, the mechanisms underlying its traversal from the circulation across the blood-brain barrier (BBB) into the subarachnoid space are poorly understood. One mechanism might involve transcytosis through microvascular endothelial cells. In this study we investigated the ability of pneumococci to invade and transmigrate through monolayers of rat and human brain microvascular endothelial cells (BMEC). Significant variability was found in the invasive capacity of clinical isolates. Phase variation to the transparent phenotype increased invasion as much as 6-fold and loss of capsule approximately 200-fold. Invasion of transparent pneumococci required choline in the pneumococcal cell wall, and invasion was partially inhibited by antagonists of the platelet-activating factor (PAF) receptor on the BMEC. Pneumococci that gained access to an intracellular vesicle from the apical side of the monolayer subsequently were subject to three fates. Most opaque variants were killed. In contrast, the transparent phase variants were able to transcytose to the basal surface of rat and human BMEC in a manner dependent on the PAF receptor and the presence of pneumococcal choline-binding protein A. The remaining transparent bacteria entering the cell underwent a previously unrecognized recycling to the apical surface. Transcytosis eventually becomes a dominating process accounting for up to 80% of intracellular bacteria. Our data suggest that interaction of pneumococci with the PAF receptor results in sorting so as to transcytose bacteria across the cell while non-PAF receptor entry shunts bacteria for exit and reentry on the apical surface in a novel recycling pathway.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of transcytosis		IMP		10041053		RGD
transcytosis		IMP		10041053		RGD

Objects Annotated

Genes (Rattus norvegicus)

Ptafr (platelet-activating factor receptor)

Additional Information