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Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes

Abstract

A common pathological characteristic of Plasmodium falciparum infection is the cytoadhesion of mature-stage-infected erythrocytes (IE) to host endothelium and syncytiotrophoblasts. Massive accumulation of IE in the brain microvasculature or placenta is strongly correlated with severe forms of malaria1. Extensive binding of IE to placental chondroitin sulfate A (CSA) is associated with physiopathology during pregnancy2,3. The adhesive phenotype of IE correlates with the appearance of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) at the erythrocyte surface (approximately 16 h after merozoite invasion), so that only early blood-stage (ring-stage) IE appear in the peripheral blood. Here, we describe results that challenge the existing view of blood-stage IE biology by demonstrating the specific adhesion of IE, during the early ring-stage, to endothelial cell lines from the brain and lung and to placental syncytiotrophoblasts. Later, during blood-stage development of these IE, trophozoites switch to an exclusively CSA cytoadhesion phenotype. Therefore, adhesion to an individual endothelial cell or syncytiotrophoblast may occur throughout the blood-stage cycle, indicating the presence in malaria patients of noncirculating (cryptic) parasite subpopulations. We detected two previously unknown parasite proteins on the surface of ring-stage IE. These proteins disappear shortly after the start of PfEMP1-mediated adhesion.

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Figure 1: Ring-stage IECSA adhesion to various cells and tissues.
Figure 2: Cytoadhesion throughout the blood-stage cycle.
Figure 3: Adhesive ring-stage IE express previously unknown ring-stage-specific surface molecules that are targets of the immune response.

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Acknowledgements

Acknowledgments We thank C. Roth for critically reading the manuscript, C. Scheidig for technical assistance, G.E. Grau, J. Sampol, and K. Muanza for human endothelial cells, and L. Edelman for the anti-CD36 FA6-152 antibody. This work was supported by grants from the Commission of the European Union for research and technical development (Contract Number CT98-0362 and QLRT-PL1999-30109), groupement de recherche and a French Army grant (Contract Number DSP/STTC-97/070). P. Buffet was supported by Fondation Mérieux and Fond d'Etudes de l'Assistance Publique/Hopitaux de Paris.

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Pouvelle, B., Buffet, P., Lépolard, C. et al. Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes . Nat Med 6, 1264–1268 (2000). https://doi.org/10.1038/81374

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