Strict Tropism for CD71+/ CD234+ Human Reticulocytes Limits Plasmodium cynomolgi's Zoonotic Potential

Varakorn Kosaisavee, Rossarin Suwanarusk, Adeline C. Y. Chua, Dennis E. Kyle, Benoit Malleret, Rou Zhang, Mallika Imwong, Rawiwan Imerbsin, Ratawan Ubalee, Hugo Sámano-Sánchez, Bryan K. S. Yeung, Jessica Ong, Eric Lombardini, François Nosten, Kevin S. W. Tan, Pablo Bifani, Georges Snounou, Laurent Rénia and Bruce Russell

Key points

  • Zoonotic <italic>P. cynomolgi</italic> switches red cell tropism for reticulocytes expressing transferrin receptor 1 (CD71+) and DARC (CD234+)

  • In the human host <italic>P. cynomolgi</italic> displays and almost identical rheopathobiology to <italic>P. vivax</italic>


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 (RBCs) indiscriminately in vitro, for 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 post-invasion morphological and rheological 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.

  • Submitted February 9, 2017.
  • Accepted June 30, 2017.