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Plasmodium falciparum cytoadherence to ICAM-1 is associated with cerebral malaria
© Craig et al; licensee BioMed Central Ltd. 2010
Published: 20 October 2010
The pathology of sever malaria is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This phenotype involves a range of host receptors and the parasite-derived variant antigen PfEMP1, which is expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these were inconclusive. In this study we measured the binding to CD36 and ICAM-1 of patient isolates from varying clinical syndromes under static and flow conditions. We also used mutant ICAM-1 proteins to characterise the key contact residues on ICAM-1 and produce a detailed binding phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion under flow conditions is raised in parasites from cerebral malaria cases. The pattern of ICAM-1 binding has also been investigated using mutant ICAM-1 proteins and indicates that isolates from severe malaria are biased towards a binding signature also seen with ITO4, a laboratory isolate selected for binding on human endothelium with similar receptor expression to that seen in the brain.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.