Vivax malaria host receptor Human malaria is caused by half a dozen species of Plasmodium protozoan parasites, each with distinctive biology. P. vivax, which causes relapsing malaria, specifically parasitizes immature red blood cells called reticulocytes. Gruszczyk et al. identified TfR1 (host transferrin receptor 1) as an alternative receptor for P. vivax. TfR1 binds to a specific P. vivax surface protein. However, the parasite that causes cerebral malaria, P. falciparum, does not share TfR1 as a receptor: P. falciparum could still infect cells in which TfR1 expression was knocked down, but P. vivax could not. Monoclonal antibodies to the P. vivax protein successfully hindered P. vivax infection of red blood cells. Science, this issue p. 48 Invasion of immature red blood cells by the malaria parasite Plasmodium vivax is mediated by binding to the host’s transferrin receptor. Plasmodium vivax shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition. We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P. vivax but not to invasion of P. falciparum. Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block P. vivax entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during P. vivax invasion.

中文翻译：

---

转铁蛋白受体 1 是间日疟原虫的网织红细胞特异性受体

间日疟宿主受体 人类疟疾是由六种疟原虫原生动物寄生虫引起的，每一种都具有独特的生物学特性。导致复发性疟疾的间日疟原虫特别寄生于称为网织红细胞的未成熟红细胞。Gruszczyk 等人。将 TfR1（宿主转铁蛋白受体 1）鉴定为间日疟原虫的替代受体。TfR1 与特定的间日疟原虫表面蛋白结合。然而，导致脑型疟疾的寄生虫恶性疟原虫不共享 TfR1 作为受体：恶性疟原虫仍可以感染 TfR1 表达被敲低的细胞，但间日疟原虫不能。间日疟原虫蛋白的单克隆抗体成功地阻止了间日疟原虫对红细胞的感染。科学，本期第 3 页。48 间日疟原虫对未成熟红细胞的侵袭是通过与宿主的转铁蛋白受体结合来介导的。间日疟原虫对网织红细胞表现出严格的宿主嗜性。我们将转铁蛋白受体 1 (TfR1) 鉴定为间日疟原虫网织红细胞结合蛋白 2b (PvRBP2b) 的受体。我们确定了参与红细胞结合的 PvRBP2b N 端结构域的结构，阐明了 TfR1 识别的分子基础。我们通过 TfR1 表达敲低分析验证了 TfR1 作为 PvRBP2b 参与的生物学靶标。缺乏 PvRBP2b 结合的 TfR1 突变细胞对间日疟原虫的入侵是顽固的，但对恶性疟原虫的入侵却没有。使用巴西和泰国的临床分离株，我们发现抑制网织红细胞结合的 PvRBP2b 单克隆抗体也能阻断 P. 间日疟原虫进入网织红细胞。这些数据表明，TfR1-PvRBP2b 入侵途径对于间日疟原虫入侵期间网织红细胞的识别至关重要。