Journal
EMBO MOLECULAR MEDICINE
Volume 11, Issue 2, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201809164
Keywords
cerebral malaria; cytoadherence; paediatric patient isolates; PfEMP1; Plasmodium falciparum
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Funding
- Wellcome Trust Investigator Award [095507]
- Danish Council for Independent Research [1333-00220, DFF-4004-00624B]
- US National Institutes of Health [NIH R01HL130678]
- College of Osteopathic Medicine, Michigan State University
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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.
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