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Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells
Published on: January 3, 2012
Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes
B Pouvelle1, P A Buffet, C Lépolard
1Laboratoire de Parasitologie Expérimentale, Faculté de Médecine, Université de la Méditerranée (Aix-Marseille II), 13385 Marseille Cedex 5, France.
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 malaria. Extensive binding of IE to placental chondroitin sulfate A (CSA) is associated with physiopathology during pregnancy. 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.
Insights
Plasmodium falciparum infected erythrocytes adhere to host cells early in infection, challenging previous views. This early adhesion involves novel parasite proteins before PfEMP1 expression, suggesting cryptic parasite subpopulations in malaria patients.
Area of Science:
- Malariology
- Cellular and Molecular Biology
- Immunology
Background:
- Plasmodium falciparum infection involves infected erythrocyte (IE) cytoadhesion to host tissues, linked to severe malaria.
- IE binding to chondroitin sulfate A (CSA) in the placenta is implicated in pregnancy-related malaria pathology.
- The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates adhesion later in the IE blood-stage cycle.
Purpose of the Study:
- To investigate the cytoadhesion properties of early-stage Plasmodium falciparum infected erythrocytes.
- To challenge the established understanding of infected erythrocyte adhesion dynamics during blood-stage development.
- To identify novel parasite proteins involved in early-stage infected erythrocyte adhesion.
Main Methods:
- Utilized endothelial cell lines from brain and lung, and placental syncytiotrophoblasts for adhesion assays.
- Characterized infected erythrocyte adhesion phenotypes throughout the blood-stage cycle.
- Detected and analyzed parasite proteins on the surface of ring-stage infected erythrocytes.
Main Results:
- Demonstrated specific adhesion of ring-stage infected erythrocytes to brain, lung, and placental endothelial cells.
- Observed a switch in adhesion phenotype, with trophozoites exclusively binding to CSA.
- Identified two novel parasite proteins on ring-stage infected erythrocytes that disappear upon PfEMP1-mediated adhesion.
Conclusions:
- Infected erythrocytes can adhere to host cells throughout the blood-stage cycle, not just in later stages.
- The findings suggest the presence of non-circulating (cryptic) parasite subpopulations in malaria patients.
- Novel parasite proteins mediate early-stage cytoadhesion, preceding PfEMP1-dependent binding.
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