Abstract
BackgroundCytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) in deep microvasculature endothelia plays a major role in the pathogenesis of cerebral malaria (CM). This biological process is thought to be mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP-1) and human receptors such as CD36 and ICAM-1. The relationship between the expression of PfEMP-1 variants and cytoadherence phenotype in the pathology of malaria is not well established.MethodsCytoadherence phenotypes of IEs to CD36, ICAM-1, CSPG and the transcription patterns of A, B, var2csa, var3, var gene groups and domain cassettes DC8 and DC13 were assessed in parasites from children with CM and uncomplicated malaria (UM) to determine if cytoadherence is related to a specific transcription profile of pfemp-1 variants.ResultsParasites from CM patients bind significantly more to CD36 than those from UM patients, but no difference was observed in their binding ability to ICAM-1 and CSPG. CM isolates highly transcribed groups A, B, var2csa, var3, DC8 and DC13 compared to UM parasites. The high transcription levels of var genes belonging to group B positively correlated with increased binding level to CD36.ConclusionCM isolates bind significantly more to CD36 than to ICAM-1, which was correlated with high transcription level of group B var genes, supporting their implication in malaria pathogenesis.
Highlights
Cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) in deep microvasculature endothelia plays a major role in the pathogenesis of cerebral malaria (CM)
Apart from chondroitin sulphate A proteoglycan (CSPG), which is the main receptor of parasites isolated from pregnant women, no definite candidate has been determined for cerebral malaria pathology [15]
The results suggest that Cluster of differentiation (CD36) is a common binding receptor used by clinical isolates from both uncomplicated malaria (UM) and CM, in agreement with earlier findings that showed the involvement of CD36 in cytoadherence [14,18,19]
Summary
Cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) in deep microvasculature endothelia plays a major role in the pathogenesis of cerebral malaria (CM). This biological process is thought to be mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP-1) and human receptors such as CD36 and ICAM-1. Post-mortem brain examination has reported high levels of ICAM-1, which co-localized with IEs in cerebral blood vessels [24]. This finding is in agreement with studies that suggested an association between disease severity and ICAM-1-binding [23]. Some studies did not detect any difference in binding to ICAM-1 in parasite isolates from severe or mild cases [20,25]
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