Dissecting erythrocyte invasion mechanisms by the malaria parasite Plasmodium falciparum.

疟疾寄生虫是顶复合体中最重要的成员，顶复合体是一个庞大而高度成功的细胞内寄生虫群。寄主细胞的入侵使顶复合体寄生虫能够在很大程度上免受寄主防御的生态位中获得丰富的营养来源。与许多其他致病性生物不同，疟原虫可以通过自身的入侵装置快速进入细胞，识别、穿透并建立自身，从而有效地感染宿主。所有顶复合体都采用这种共同的宿主细胞进入模式，但个别物种具有独特的特征，并利用一套特定的配体-受体相互作用。细胞外疟疾分裂子侵入红细胞是一个重要的多步骤过程，快速有效地进入宿主细胞的发展对这些病原体的进化成功至关重要。Merozoite的入侵开始于最初与红细胞的低亲和力附着，随后在快速进入之前与红细胞膜重新定位以对抗寄生虫的顶极。成功入侵的关键是两个细胞之间紧密连接的建立，在红细胞进入时，两个细胞之间的紧密连接点沿着入侵的裂殖子的长度前进。这个连接点为分裂子侵入马达提供了一个牵引力点，允许寄生虫自己进入红细胞。随着入侵的进行，红细胞膜向内弯曲，形成一个最初的入侵坑和随后的寄生液泡，一个寄生虫在其红细胞周期内移动和居住的空间。随着寄生虫底部紧密连接的关闭，将液泡膜和红细胞膜与外部环境隔离，进入完成。我们的实验室有兴趣剖析这个有趣的生物过程背后的机制。

The malaria parasite is the most important member of the Apicomplexa, a large and highly successful group of intracellular parasites. Invasion of host cells allows apicomplexan parasites access to a rich source of nutrients in a niche that is largely protected from host defenses. In contrast to many other pathogenic organisms, Plasmodium spp. can efficiently infect their hosts by rapidly gaining entry to cells using their own invasion apparatus to identify, penetrate, and establish themselves. All Apicomplexa adopt this common mode of host-cell entry but individual species incorporate unique features and utilize a specific set of ligand-receptor interactions. Invasion into an erythrocyte by the extracellular malaria merozoite is an essential multistep process and development of rapid and efficient entry into the host cell has been important in the evolutionary success of these pathogens. Merozoite invasion begins with an initial low affinity attachment to the erythrocyte followed by reorientation to oppose the parasite apical pole with the erythrocyte membrane prior to rapid entry. Critical to successful invasion is the establishment of a tight junction, a point of close apposition between the two cells that progresses along the length of the invading merozoite during erythrocyte entry. This junction provides a point of traction for the merozoite invasion motor, allowing the parasite to drive itself into the erythrocyte. As invasion proceeds the erythrocyte membrane buckles inwards, forming an initial invasion pit and subsequent parasitophorous vacuole, a space into which the parasite moves and resides for the duration of its intraerythrocytic cycle. Entry is completed with the tight junction closing at the base of the parasite, sealing the vacuolar and erythrocyte membranes from the external environment. Our laboratory is interested in dissecting the mechanisms behind this intriguing biological process.