Strict tropism for CD71/CD234 human reticulocytes limits the zoonotic potential of .

Two malaria parasites of Southeast Asian macaques, and , 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 has been found in humans. In this study, we show that whereas 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 -infected human reticulocytes that are strikingly similar to those observed for These observations stress the value of as a model in the development of blood stage vaccines against vivax malaria.