title: Glycophorin C (CD236R) mediates vivax malaria parasite rosetting to normocytes.
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.
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;
authors.forename: Wenn-Chyau
authors.initials: WC
authors.lastname: Lee
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.forename: Yee-Ling
authors.initials: YL
authors.lastname: Lau
authors.forename: Marjorie
authors.initials: M
authors.lastname: Mauduit
authors.forename: Mun-Yik
authors.initials: MY
authors.lastname: Fong
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Cho
authors.forename: Rossarin
authors.initials: R
authors.lastname: Suwanarusk
authors.forename: Rou
authors.initials: R
authors.lastname: Zhang
authors.forename: Letusa
authors.initials: L
authors.lastname: Albrecht
authors.forename: Fabio T M
authors.initials: FT
authors.lastname: Costa
authors.forename: Peter
authors.initials: P
authors.lastname: Preiser
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.forename: Bruce
authors.initials: B
authors.lastname: Russell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006021:Glycophorins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016780:Malaria, Vivax / Q000175:diagnosis / Q000378:metabolism* / Q000469:parasitology; D010966:Plasmodium vivax / Q000276:immunology* / Q000302:isolation & purification; D017463:Receptors, Complement 3b / Q000037:antagonists & inhibitors; D012397:Rosette Formation / Q000379:methods*; D057188:Workflow
chemical_list: D000911:Antibodies, Monoclonal; D006021:Glycophorins; D017463:Receptors, Complement 3b