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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

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Sequestration of Plasmodium falciparum-infected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNF-activated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAM-1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature.

Original languageEnglish
JournalEMBO Molecular Medicine
Volume11
Issue number2
ISSN1757-4676
DOIs
Publication statusPublished - Feb 2019

    Research areas

  • Brain/parasitology, Cell Adhesion, Cells, Cultured, Child, Child, Preschool, Endothelial Cells/physiology, Erythrocytes/parasitology, Female, Humans, Infant, Malaria, Cerebral/parasitology, Male, Models, Biological, Plasmodium falciparum/growth & development

ID: 59422124