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Cytoadherence and virulence - the case of Plasmodium knowlesi malaria

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1475_2875_11_33.pdf (1.509Mb)
Date
03/02/2012
Author
Fatih, Farrah A.
Siner, Angela
Ahmed, Atique
Woon, Lu Chan
Craig, Alister G.
Singh, Balbir
Krishna, Sanjeev
Cox Singh, Janet
Keywords
RB Pathology
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Abstract
Background: Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. Methods: Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37 degrees C for one hour the dishes were washed and the number of infected erythrocytes bound/mm(2) to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. Results: Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 +/- 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 +/- 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. Conclusions: Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.
Citation
Fatih , F A , Siner , A , Ahmed , A , Woon , L C , Craig , A G , Singh , B , Krishna , S & Cox Singh , J 2012 , ' Cytoadherence and virulence - the case of Plasmodium knowlesi malaria ' , Malaria Journal , vol. 11 , 33 . https://doi.org/10.1186/1475-2875-11-33
Publication
Malaria Journal
Status
Peer reviewed
DOI
https://doi.org/10.1186/1475-2875-11-33
ISSN
1475-2875
Type
Journal article
Rights
© 2012 Fatih et al; licensee 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.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/3873

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