Glycophorin C (CD236R) mediates vivax malaria parasite rosetting to normocytes

Blood. 2014 May 1;123(18):e100-9. doi: 10.1182/blood-2013-12-541698. Epub 2014 Mar 20.

Abstract

Rosetting phenomenon has been linked to malaria pathogenesis. Although rosetting occurs in all causes of human malaria, most data on this subject has been derived from Plasmodium falciparum. Here, we investigate the function and factors affecting rosette formation in Plasmodium vivax. To achieve this, we used a range of novel ex vivo protocols to study fresh and cryopreserved P vivax (n = 135) and P falciparum (n = 77) isolates from Thailand. Rosetting is more common in vivax than falciparum malaria, both in terms of incidence in patient samples and percentage of infected erythrocytes forming rosettes. Rosetting to P vivax asexual and sexual stages was evident 20 hours postreticulocyte invasion, reaching a plateau after 30 hours. Host ABO blood group, reticulocyte count, and parasitemia were not correlated with P vivax rosetting. Importantly, mature erythrocytes (normocytes), rather than reticulocytes, preferentially form rosetting complexes, indicating that this process is unlikely to directly facilitate merozoite invasion. Although antibodies against host erythrocyte receptors CD235a and CD35 had no effect, Ag-binding fragment against the BRIC 4 region of CD236R significantly inhibited rosette formation. Rosetting assays using CD236R knockdown normocytes derived from hematopoietic stem cells further supports the role of glycophorin C as a receptor in P vivax rosette formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Cryopreservation / methods
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology*
  • Erythrocytes / pathology
  • Gene Knockdown Techniques
  • Glycophorins / genetics
  • Glycophorins / immunology
  • Glycophorins / metabolism*
  • Humans
  • Malaria, Vivax / diagnosis
  • Malaria, Vivax / metabolism*
  • Malaria, Vivax / parasitology
  • Plasmodium vivax / immunology*
  • Plasmodium vivax / isolation & purification
  • Receptors, Complement 3b / antagonists & inhibitors
  • Rosette Formation / methods*
  • Workflow

Substances

  • Antibodies, Monoclonal
  • Glycophorins
  • Receptors, Complement 3b