ArticleThe Journal of clinical investigation1998
Pneumococcal trafficking across the blood-brain barrier. Molecular analysis of a novel bidirectional pathway.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
160 citing papers in PubMed, 1 synthesis or guideline pooled it, 385 citations in OpenAlex.
- Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2010Pooled it
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- Blood-brain barrier dysfunction in intensive care unit.Journal of intensive medicine · 2023Review
- Acute organ injury and long-term sequelae of severe pneumococcal infections.Pneumonia (Nathan Qld.) · 2023Review
- The oxidative stress response ofFrontiers in microbiology · 2023Review
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- Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.Science advances · 2022Article
- Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies.Frontiers in cellular and infection microbiology · 2022Review
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- Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid.Frontiers in microbiology · 2022Article
- Effect of stimulated platelets in COVID-19 thrombosis: Role of alpha7 nicotinic acetylcholine receptor.Frontiers in cardiovascular medicine · 2022Review
- A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis ofFrontiers in cellular and infection microbiology · 2022Review
- Pyruvate Oxidase as a Key Determinant of Pneumococcal Viability during Transcytosis across Brain Endothelium.Journal of bacteriology · 2021Article
- The semantics of microglia activation: neuroinflammation, homeostasis, and stress.Journal of neuroinflammation · 2021Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.