Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites.
Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites.
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DOI：
10.7554/elife.61516
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发表时间：
2021-05-24
期刊：
影响因子：
7.7
通讯作者：
Egan ES
中科院分区：
文献类型：
--
作者：
Shakya B;Patel SD;Tani Y;Egan ES
疟疾寄生虫恶性疟原虫侵入人类红细胞是一个多步骤的过程。以前，恶性疟原虫宿主因子的正向遗传筛选确定红细胞CD 55是入侵所必需的，但其具体作用以及它如何与介导这一复杂过程的其他因子相互作用尚不清楚。使用CRISPR-Cas9编辑，基于抗体的抑制和活细胞成像，我们在这里证明了CD 55是寄生虫内化所必需的。前入侵动力学，红细胞变形能力，和棘红细胞没有受到CD 55的影响，但进入抑制时，CD 55被阻断或缺席。可视化的寄生虫连接到CD 55-空红细胞点的作用，CD 55的稳定性和/或进展的移动连接。我们的研究结果表明，CD 55的行为后，放电的寄生虫的棒状细胞器，并发挥独特的作用，相对于所有其他入侵受体。由于对CD 55的需求是应变超越的，这些结果表明，CD 55或其相互作用的合作伙伴可能持有作为疟疾的治疗靶点的潜力。
Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum is a multi-step process. Previously, a forward genetic screen for P. falciparum host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization. Pre-invasion kinetics, erythrocyte deformability, and echinocytosis were not influenced by CD55, but entry was inhibited when CD55 was blocked or absent. Visualization of parasites attached to CD55-null erythrocytes points to a role for CD55 in stability and/or progression of the moving junction. Our findings demonstrate that CD55 acts after discharge of the parasite’s rhoptry organelles, and plays a unique role relative to all other invasion receptors. As the requirement for CD55 is strain-transcendent, these results suggest that CD55 or its interacting partners may hold potential as therapeutic targets for malaria.