Cytoadherence and virulence - the case of Plasmodium knowlesi malaria

Malaria Journal

Research

Farrah A Fatih¹  Janet Cox-Singh²  Sanjeev Krishna²  Angela Siner³  Balbir Singh³  Atique Ahmed³  Alister G Craig⁴  Lu Chan Woon⁵ 

[1] Centre for Infection and Immunity, St George's University of London, SW17 0RE, London, UK;Centre for Infection and Immunity, St George's University of London, SW17 0RE, London, UK;Malaria Research Centre, University Malaysia Sarawak, 93150, Kuching, Malaysia;Malaria Research Centre, University Malaysia Sarawak, 93150, Kuching, Malaysia;Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, L3 5QA, Liverpool, UK;Pathology Laboratory, Hospital Sarikei, 96100, Sarikei, Malaysia;

关键词: P. knowlesi;    Cytoadherence;    SICAvar;    ICAM-1;    VCAM;    CD36;    Malaria;    Coma;   

DOI  :  10.1186/1475-2875-11-33

 received in 2011-11-17, accepted in 2012-02-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundCytoadherence 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.MethodsFive 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°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 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.ResultsBlood 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.ConclusionsPlasmodium 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.

【 授权许可】

Unknown   
© Fatih et al; licensee BioMed Central Ltd. 2012. 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.