Cytoadherence phenotype of Plasmodium falciparum-infected erythrocytes is associated with specific pfemp-1 expression in parasites from children with cerebral malaria

Abstract

Background: 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. The relationship between the expression of PfEMP-1 variants and cytoadherence phenotype in the pathology of malaria is not well established.

Methods: Cytoadherence 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.

Results: Parasites 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.

Conclusion: CM 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.

Figure 1

Binding level (number of bound IEs/mm ² ) of CM and UM isolates on CSPG, ICAM-1 and CD36. The difference in binding levels to a specific receptor was tested by the Mann-Whitney U test, significant P-value is shown in the figure.

Figure 2

Transcript abundances of var genes from group A, B, var2csa and var3 in Plasmodium falciparum isolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns of specific var genes were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.

Figure 3

Transcript abundances of DC8 and DC13 targeted by CIDRα1.1, DBLβ12, DBLα1.7, and CIDRα1.4 primers in Plasmodium falciparum isolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.