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

• Main Authors: Wenn Chyau Lee, Benoit Malleret, Yee Ling Lau, Marjorie Mauduit, Mun Yik Fong, Jee Sun Cho, Rossarin Suwanarusk, Rou Zhang, Letusa Albrecht, Fabio T M Costa, Peter Preiser, Rose McGready, Laurent Renia, Francois Nosten, Bruce Russell
• Other Authors: University of Malaya
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology; Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/33268
• Institution: Mahidol University

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 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.