CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts
CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts
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DOI：
10.1111/j.1365-2958.2005.05024.x
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发表时间：
2006-03-01
影响因子：
3.6
通讯作者：
Yuda, M
中科院分区：
文献类型：
--
作者：
Kariu, T;Ishino, T;Yuda, M
疟疾寄生虫在其生命周期中有两个宿主，脊椎动物和蚊子。我们在这里报告，疟疾入侵到这些主机介导的蛋白质，指定的细胞穿越蛋白的动合子和子孢子（CelTOS），这是本地化的寄生虫侵入运动的细胞器的微丝。靶向破坏伯氏疟原虫中的CelTOS基因使蚊子宿主中的寄生虫感染性降低约200倍。破坏也降低了子孢子在肝脏中的感染性，几乎消除了其细胞通过能力。肝脏感染性恢复枯否细胞耗竭大鼠，表明CelTOS是必要的子孢子通道从循环系统到肝细胞通过肝窦细胞层。电子显微镜分析显示，celtos破坏动合子侵入中肠上皮细胞的细胞膜破裂，但随后未能穿过细胞，表明CelTOS是必要的迁移通过细胞质。这些结果表明，子孢子和动合子都使用保守的细胞传代机制来突破宿主细胞屏障。阐明这些机制可能会导致新的抗疟策略，以阻止寄生虫的传播。
The malarial parasite has two hosts in its life cycle, a vertebrate and a mosquito. We report here that malarial invasion into these hosts is mediated by a protein, designated cell-traversal protein for ookinetes and sporozoites (CelTOS), which is localized to micronemes that are organelles for parasite invasive motility. Targeted disruption of the CelTOS gene in Plasmodium berghei reduced parasite infectivity in the mosquito host approximately 200-fold. The disruption also reduced the sporozoite infectivity in the liver and almost abolished its cell-passage ability. Liver infectivity was restored in Kupffer cell-depleted rats, indicating that CelTOS is necessary for sporozoite passage from the circulatory system to hepatocytes through the liver sinusoidal cell layer. Electron microscopic analysis revealed that celtos-disrupted ookinetes invade the midgut epithelial cell by rupturing the cell membrane, but then fail to cross the cell, indicating that CelTOS is necessary for migration through the cytoplasm. These results suggest that conserved cell-passage mechanisms are used by both sporozoites and ookinetes to breach host cellular barriers. Elucidation of these mechanisms might lead to novel antimalarial strategies to block parasite's transmission.