Characterisation of Plasmodium falciparum populations selected on the human endothelial receptors P-selectin, E-selectin, CD9 and CD151

Nahla Galal Metwally,Iris Bruchhaus,Stephan Lorenzen,Pedro Lubiana,Thomas Gutsmann,Kathrin Schuldt,Anna Bachmann,Lisa K Roth,Egbert Tannich,Susanne Witt,Henning Tidow,Thomas Roeder,Thorsten Burmester,Ann-Kathrin Tilly,Michael Dörpinghaus

doi:10.1038/s41598-017-04241-3

Abstract

The ability of the parasite Plasmodium falciparum to evade the immune system and be sequestered within human small blood vessels is responsible for severe forms of malaria. The sequestration depends on the interaction between human endothelial receptors and P. falciparum erythrocyte membrane protein 1 (PfEMP1) exposed on the surface of the infected erythrocytes (IEs). In this study, the transcriptomes of parasite populations enriched for parasites that bind to human P-selectin, E-selectin, CD9 and CD151 receptors were analysed. IT4_var02 and IT4_var07 were specifically expressed in IT4 parasite populations enriched for P-selectin-binding parasites; eight var genes (IT4_var02/07/09/13/17/41/44/64) were specifically expressed in isolate populations enriched for CD9-binding parasites. Interestingly, IT4 parasite populations enriched for E-selectin- and CD151-binding parasites showed identical expression profiles to those of a parasite population exposed to wild-type CHO-745 cells. The same phenomenon was observed for the 3D7 isolate population enriched for binding to P-selectin, E-selectin, CD9 and CD151. This implies that the corresponding ligands for these receptors have either weak binding capacity or do not exist on the IE surface. Conclusively, this work expanded our understanding of P. falciparum adhesive interactions, through the identification of var transcripts that are enriched within the selected parasite populations.

Highlights

Plasmodium falciparum is responsible for most of the morbidity and mortality accompanying malaria in humans
The current study aimed to identify the as yet unknown ligands of P. falciparum that interact with the human receptors P-selectin, E-selectin, CD9 and CD151
To identify the putative PfEMP1 ligands responsible for infected erythrocytes (IEs) binding to various human receptors, the receptors were expressed on the surface of CHO-745 cells, and transcriptomes of ring-stage parasite populations enriched for parasites binding to these receptors were analysed

Summary

Introduction

Plasmodium falciparum is responsible for most of the morbidity and mortality accompanying malaria in humans. The ability of P. falciparum-infected erythrocytes (IEs) to evade the immune system and be sequestered in small blood vessels of vital organs constitutes the major virulence attribute[2, 3]. The success of P. falciparum as a parasite of humans is attributed to the presence of variant surface antigens (VSAs) on the IE surface. These antigens are encoded by five large multi-copy gene families, namely, the var, rif (repetitive interspersed family), stevor (subtelomeric variable open read frame), surf PfEMP1 proteins can be classified into groups A, B, B/A, C, B/C or E, depending on the chromosomal localisation of the encoding gene, the upstream sequences and PfEMP1 domain composition[8, 21,22,23]. Interactions with only a few human endothelial receptors, CD36, intercellular adhesion molecule-1 (ICAM-1) and endothelial protein C receptor (EPCR), have been studied in detail

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Conclusion