Erythrocyte CD55 facilitates the internalization of Plasmodium falciparum parasites

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 point to a role for CD55 in 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.

恶性疟原虫入侵人类红细胞是一个多步骤的过程。此前，对恶性疟原虫宿主因子的正向遗传筛选确定红细胞CD55对入侵至关重要，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。通过使用CRISPR - Cas9编辑、基于抗体的抑制和活细胞成像，我们在此表明CD55是寄生虫内化所特需的。入侵前的动力学、红细胞变形性和棘状红细胞增多症不受CD55影响，但当CD55被阻断或缺失时，入侵会受到抑制。对附着在CD55缺失红细胞上的寄生虫的观察表明CD55在移动连接的进展中起作用。我们的研究结果表明，CD55在寄生虫的棒状体细胞器释放后起作用，并且相对于所有其他入侵受体发挥着独特的作用。由于对CD55的需求是超越菌株的，这些结果表明CD55或其相互作用的伙伴可能具有作为疟疾治疗靶点的潜力。