Plasmodium vivax is the most prevalent parasite species that causes malaria in humans and exclusively infects reticulocytes. Reticulocyte infection is facilitated by P vivax Duffy binding protein (DBP), which utilizes DARC (Duffy antigen receptor for chemokines) as an entry point. However, the selective tropism of P vivax for transferrin receptor (CD71)-positive reticulocytes remained unexplained, given the constitutive expression of DARC during reticulocyte maturation. CD71/RNA double staining of reticulocytes enriched from adult peripheral blood reveals 4 distinct reticulocyte populations: CD71^high/RNA^high (∼0.016%), CD71^low/RNA^high (∼0.059%), CD71^neg/RNA^high (∼0.37%), CD71^neg/RNA^low (∼0.55%), and erythrocytes CD71^neg/RNA^neg (∼99%). We hypothesized that selective association of DBP with a small population of immature reticulocytes could explain the preference of P vivax for reticulocytes. Binding of specific monoclonal anti-DARC antibodies and recombinant DBP to CD71^high/RNA^high reticulocytes was significantly higher compared with other reticulocyte populations and erythrocytes. Interestingly, the total DARC protein throughout reticulocyte maturation was constant. The data suggest that selective exposure of the DBP binding site within DARC is key to the preferential binding of DBP to immature reticulocytes, which is the potential mechanism underlying the preferential infection of a reticulocyte subset by P vivax.

间日疟原虫是最普遍的寄生虫物种，可在人类中引起疟疾并仅感染网织红细胞。间质细胞达菲结合蛋白（DBP）促进了网状细胞感染，该蛋白利用DARC（趋化因子的达菲抗原受体）作为切入点。然而，鉴于网织红细胞成熟过程中DARC的组成型表达，P间体对转铁蛋白受体（CD71）阳性网织红细胞的选择性趋向性尚无法解释。从成人外周血富集的网状细胞的CD71 / RNA双重染色揭示了4个不同的网状细胞群体：CD71^高/ RNA^高（〜0.016％），CD71^低/ RNA^高（〜0.059％），CD71 ^neg/ RNA^高（〜0.37％），CD71^负/ RNA^低（〜0.55％）和红细胞CD71 ^neg / RNA^负（〜99％）。我们假设DBP与少量未成熟网织细胞的选择性结合可以解释P间质对网织细胞的偏好。特异性单克隆抗DARC抗体和重组DBP与CD71^高/ RNA^高的结合网织红细胞明显高于其他网织红细胞和红细胞。有趣的是，整个网织红细胞成熟过程中的总DARC蛋白是恒定的。数据表明，在DARC中选择性暴露DBP结合位点是DBP优先结合未成熟网织红细胞的关键，这是潜在的机制，是间日疟原虫优先感染网织红细胞亚群的基础。