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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Severe malaria is associated with parasite binding to endothelial protein C receptor
Nature, Volume 498, No. 7455, Year 2013
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Description
Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions. © 2013 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Turner, Louise
Denmark, Copenhagen
Københavns Universitet
Lavstsen, Thomas
Denmark, Copenhagen
Københavns Universitet
Berger, Sanne Schou
Denmark, Copenhagen
Københavns Universitet
Wang, Christian William
Denmark, Copenhagen
Københavns Universitet
Petersen, Jens Emil Vang
Denmark, Copenhagen
Københavns Universitet
Avril, Marion
United States, Seattle
Seattle Biomedical Research Institute
Brazier, Andrew J.
United States, Seattle
Seattle Biomedical Research Institute
Freeth, Jim
United Kingdom, High Peak
Retrogenix Ltd
Jespersen, Jakob S.
Denmark, Copenhagen
Københavns Universitet
Nielsen, M. A.
Denmark, Copenhagen
Københavns Universitet
Magistrado, Pamela A.
Tanzania
National Institute for Medical Research Tanzania
Lusingu, John Peter Andrea
Tanzania
National Institute for Medical Research Tanzania
Smith, Joseph D.
United States, Seattle
Seattle Biomedical Research Institute
United States, Seattle
University of Washington
Higgins, Matthew K.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
G. Theander, Thor Grundtvig
Denmark, Copenhagen
Københavns Universitet
Statistics
Citations: 489
Authors: 15
Affiliations: 6
Identifiers
Doi:
10.1038/nature12216
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Infectious Diseases
Maternal And Child Health