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.

Nature Medicine
|November 4, 2000
PubMed

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.