Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

• Published in: Blood Vol. 130; no. 11; pp. 1357 - 1363
• Main Authors: Kosaisavee, Varakorn, Suwanarusk, Rossarin, Chua, Adeline C.Y., Kyle, Dennis E., Malleret, Benoit, Zhang, Rou, Imwong, Mallika, Imerbsin, Rawiwan, Ubalee, Ratawan, Sámano-Sánchez, Hugo, Yeung, Bryan K.S., Ong, Jessica J.Y., Lombardini, Eric, Nosten, François, Tan, Kevin S.W., Bifani, Pablo, Snounou, Georges, Rénia, Laurent, Russell, Bruce
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-09-2017; American Society of Hematology
• Subjects: Animals; Antigens, CD - metabolism; Duffy Blood-Group System - metabolism; Erythrocytes - parasitology; Host-Parasite Interactions; Humans; Life Sciences; Macaca; Merozoites - physiology; Plasmodium cynomolgi - physiology; Plasmodium vivax - physiology; Receptors, Cell Surface - metabolism; Receptors, Transferrin - metabolism; Red Cells, Iron, and Erythropoiesis; Reticulocytes - parasitology; Rheology; Tropism; Zoonoses - parasitology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2017-02-764787

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi–infected human reticulocytes that are strikingly similar to those observed for P vivax. These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.
•Zoonotic P cynomolgi switches red cell tropism for reticulocytes expressing Trf1 (CD71+) and DARC (CD234+).•In the human host, P cynomolgi displays an almost identical rheopathobiology to P vivax.