Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Storm, J. et al. (2019) Cerebral malaria is associated with differential cytoadherence to brain endothelial cells. EMBO Molecular Medicine, 11(2), e9164. (doi: 10.15252/emmm.201809164) (PMID:30610112) (PMCID:PMC6365927)

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Abstract

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.

Item Type:Articles
Additional Information:This work was funded by a Wellcome Trust Investigator Award to AGC (grant 095507), Danish Council for Independent Research (grants 1333-00220 and DFF– 4004-00624B) and US National Institutes of Health (NIH R01HL130678) (TK, CW, JJ) and internal support from the College of Osteopathic Medicine, Michigan State University (TT, KS).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Moxon, Dr Christopher
Authors: Storm, J., Jespersen, J. S., Seydel, K. B., Szestak, T., Mbewe, M., Chisala, N. V., Phula, P., Wang, C. W., Taylor, T. E., Moxon, C. A., Lavstsen, T., and Craig, A. G.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:EMBO Molecular Medicine
Publisher:Wiley
ISSN:1757-4676
ISSN (Online):1757-4684
Published Online:03 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in EMBO Molecular Medicine 11(2): e9164
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
525071Cytoadherence-mediated pathology in cerebral malariaJames BrewerWellcome Trust (WELLCOTR)095507/Z/11/ZIII -IMMUNOLOGY