Evidence map›Paper›PMID 24343658›Full record

ArticleInfection and immunity2014

Rosetting Plasmodium falciparum-infected erythrocytes bind to human brain microvascular endothelial cells in vitro, demonstrating a dual adhesion phenotype mediated by distinct P. falciparum erythrocyte membrane protein 1 domains.

Yvonne Adams, Pongsak Kuhnrae, Matthew K Higgins, Ashfaq Ghumra, J Alexandra Rowe

Abstract read
In one paragraph

Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed.

  1. Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Mechanism of Immune Evasion in Mosquito-Borne Diseases.Pathogens (Basel, Switzerland) · 2023
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. eLife · 2020
    Article
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yvonne AdamsCentre for Immunity, Infection and Evolution, Institute of Infection and Immunity, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Pongsak Kuhnrae
Matthew K Higgins
Ashfaq Ghumra
J Alexandra Rowe

Funding

Wellcome Trust 084226Wellcome Trust 095831
6 · The paper itself

Abstract

Adhesion interactions between Plasmodium falciparum-infected erythrocytes (IE) and human cells underlie the pathology of severe malaria. IE cytoadhere to microvascular endothelium or form rosettes with uninfected erythrocytes to survive in vivo by sequestering IE in the microvasculature and avoiding splenic clearance mechanisms. Both rosetting and cytoadherence are mediated by the parasite-derived IE surface protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting and cytoadherence have been widely studied as separate entities; however, the ability of rosetting P. falciparum strains to cytoadhere has received little attention. Here, we show that IE of the IT/R29 strain expressing a rosette-mediating PfEMP1 variant (IT4var09) cytoadhere in vitro to a human brain microvascular endothelial cell line (HBEC-5i). Cytoadherence was inhibited by heparin and by treatment of HBEC-5i with heparinase III, suggesting that the endothelial receptors for IE binding are heparan sulfate proteoglycans. Antibodies to the N-terminal regions of the IT4var09 PfEMP1 variant (NTS-DBL1α and DBL2γ domains) specifically inhibited and reversed cytoadherence down to low concentrations (<10 μg/ml of total IgG). Surface plasmon resonance experiments showed that the NTS-DBLα and DBL2γ domains bind strongly to heparin, with half-maximal binding at a concentration of ∼0.5 μM in both cases. Therefore, cytoadherence of IT/R29 IE is distinct from rosetting, which is primarily mediated by NTS-DBL1α interactions with complement receptor 1. These data show that IT4var09-expressing parasites are capable of dual interactions with both endothelial cells and uninfected erythrocytes via distinct receptor-ligand interactions.

Indexed as

BrainCell AdhesionCell LineEndothelial CellsEndothelium, VascularErythrocyte MembraneErythrocytesHumansLigandsMalaria, FalciparumMembrane ProteinsPlasmodium falciparumProtozoan ProteinsRosette Formationerythrocyte membrane protein 1, Plasmodium falciparumLigandsMembrane ProteinsProtozoan Proteins

Identifiers

PMID24343658
PMCPMC3958005

What OpenQuestion holds

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Registered trials

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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.