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EMBO Mol Med. 2019 Jan 3. pii: e9164. doi: 10.15252/emmm.201809164. [Epub ahead of print]

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.

Author information

1
Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK janet.storm@lstmed.ac.uk Alister.Craig@lstmed.ac.uk.
2
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
3
College of Medicine, University of Malawi, Blantyre, Malawi.
4
Department of International Health, Immunology & Microbiology, Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
5
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
6
Blantyre Malaria Project, College of Medicine, University of Malawi, Blantyre, Malawi.
7
Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
8
Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK.
9
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
10
Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.

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.

KEYWORDS:

Plasmodium falciparum ; PfEMP1; cerebral malaria; cytoadherence; paediatric patient isolates

PMID:
30610112
DOI:
10.15252/emmm.201809164
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