Wenn Chyau LeeBenoit MalleretYee Ling LauMarjorie MauduitMun Yik FongJee Sun ChoRossarin SuwanaruskRou ZhangLetusa AlbrechtFabio T M CostaPeter PreiserRose McGreadyLaurent ReniaFrancois NostenBruce RussellUniversity of MalayaNational University of SingaporeAgency for Science, Technology and Research, SingaporeUniversidade Estadual de CampinasNanyang Technological UniversityMahidol UniversityNuffield Department of Clinical Medicine2018-11-092018-11-092014-05-01Blood. Vol.123, No.18 (2014)15280020000649712-s2.0-84900440031https://repository.li.mahidol.ac.th/handle/20.500.14594/33268Rosetting 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 Plasmodiumvivax. To achieve this, we used a range of novel ex vivo protocols to study fresh and cryopreserved P vivax (n5 135) and P falciparum(n5 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 ABOblood 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. © 2014 by The American Society of Hematology.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineArticleSCOPUS10.1182/blood-2013-12-541698