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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Plasmodium falciparum Expressing Domain Cassette 5 Type PfEMP1 (DC5-PfEMP1) Bind PECAM1
PLoS ONE, Volume 8, No. 7, Article e69117, Year 2013
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Description
Members of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1) family expressed on the surface of malaria-infected erythrocytes mediate binding of the parasite to different receptors on the vascular lining. This process drives pathologies, and severe childhood malaria has been associated with the expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into subtypes based on upstream sequences and the presence of semi-conserved PfEMP1 domain compositions named domain cassettes (DCs). Earlier studies have indicated that DC5-containing PfEMP1 (DC5-PfEMP1) are more likely to be expressed in children with severe malaria disease than in children with uncomplicated malaria, but these PfEMP1 subtypes only dominate in a relatively small proportion of the children with severe disease. In this study, we have characterised the genomic sequence characteristic for DC5, and show that two genetically different parasite lines expressing DC5-PfEMP1 bind PECAM1, and that anti-DC5-specific antibodies inhibit binding of DC5-PfEMP1-expressing parasites to transformed human bone marrow endothelial cells (TrHBMEC). We also show that antibodies against each of the four domains characteristic for DC5 react with native PfEMP1 expressed on the surface of infected erythrocytes, and that some of these antibodies are cross-reactive between the two DC5-containing PfEMP1 molecules tested. Finally, we confirm that anti-DC5 antibodies are acquired early in life by individuals living in malaria endemic areas, that individuals having high levels of these antibodies are less likely to develop febrile malaria episodes and that the antibody levels correlate positively with hemoglobin levels. © 2013 Berger et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3706608/bin/pone.0069117.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3706608/bin/pone.0069117.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3706608/bin/pone.0069117.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3706608/bin/pone.0069117.s004.tif
Authors & Co-Authors
Berger, Sanne Schou
Denmark, Copenhagen
Rigshospitalet
Turner, Louise
Denmark, Copenhagen
Rigshospitalet
Wang, Christian William
Denmark, Copenhagen
Rigshospitalet
Petersen, Jens Emil Vang
Denmark, Copenhagen
Rigshospitalet
Kraft, Maria
Denmark, Copenhagen
Rigshospitalet
Lusingu, John Peter Andrea
Tanzania
National Institute for Medical Research Tanzania
Mmbando, Bruno P.
Tanzania
National Institute for Medical Research Tanzania
Marquard, Andrea Marion
Denmark, Copenhagen
Rigshospitalet
Bengtsson, Dominique C.
Denmark, Copenhagen
Rigshospitalet
Hviid, Lars
Denmark, Copenhagen
Rigshospitalet
Nielsen, M. A.
Denmark, Copenhagen
Rigshospitalet
G. Theander, Thor Grundtvig
Denmark, Copenhagen
Rigshospitalet
Lavstsen, Thomas
Denmark, Copenhagen
Rigshospitalet
Statistics
Citations: 46
Authors: 13
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0069117
e-ISSN:
19326203
Research Areas
Infectious Diseases
Maternal And Child Health