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.

东南亚猕猴的两种疟疾寄生虫，诺氏疟原虫和食蟹猴P可以通过实验感染人类。在这两种物种都常见的马来西亚，人畜共患的诺氏疟疾最近已成为主要疾病，整个区域都有病例记录。相比之下，迄今为止，在人类中仅发现了一例自然获得的食蟹猴。在这项研究中，我们证明了P食蟹猴裂殖子在体外无差别地侵入猴红细胞，在人类中，它们仅限于表达转铁蛋白受体1（Trf1或CD71）和达菲抗原/趋化因子受体（DARC或CD234）的网织红细胞。这很可能导致可检测到的人畜共患的食蟹猴疟疾的缺乏。我们进一步描述了食蟹猕猴感染的人类网织细胞的侵袭后形态学和流变学变化，与观察到的间日疟原虫惊人地相似。这些观察结果强调了食蟹猕猴（P cynomolgi）作为抗间日疟疾血液阶段疫苗开发模型的价值。