Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.

Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.
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DOI:
10.1038/nature13242
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发表时间:
2014-04-24
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
文献类型:
--
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溶组织内阿米巴是阿米巴病的病原体,阿米巴病是发展中国家一种潜在致命的腹泻病。这种寄生虫因其破坏宿主组织的能力而被命名为“histolytica”,这很可能是由直接杀死人体细胞驱动的。人类细胞杀死的机制尚不清楚,但公认的模型是寄生虫在摄入前利用分泌的毒性效应物杀死细胞。在这里,我们报告了一个令人惊讶的发现,阿米巴变形虫通过咬断和摄取不同的活人类细胞碎片来杀死细胞,导致细胞内钙升高并最终细胞死亡。细胞杀死后,阿米巴原虫分离并停止摄取。吞咽叮咬是杀死细胞所必需的,也有助于侵入肠道组织。人类活细胞咬伤的内化让人想起在免疫细胞之间观察到的 trogocytosis(希腊语 trogo-,蚕食),但阿米巴 trogocytosis 有所不同,因为它会导致死亡。活细胞材料的摄入和尸体的排斥与多细胞生物中已建立的死细胞清除模型形成鲜明对比。这些发现改变了阿米巴病中组织破坏的范式,并表明吞噬作用的古老起源是细胞间交换的一种形式。
Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrheal disease in the developing world. The parasite was named “histolytica” for its ability to destroy host tissues, which is most likely driven by direct killing of human cells. The mechanism of human cell killing has been unclear, though the accepted model was that the parasites use secreted toxic effectors to kill cells prior to ingestion. Here we report the surprising discovery that amoebae kill by biting off and ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. After cell killing, amoebae detach and cease ingestion. Ingestion of bites is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of bites of living human cells is reminiscent of trogocytosis (Greek trogo–, nibble) observed between immune cells, but amoebic trogocytosis differs since it results in death. The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms. These findings change the paradigm for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.
TC21和RHOG GTPase依赖性吞噬作用介导了免疫突触的T细胞受体内在化。
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发表时间: 2010-06-28
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影响因子: --
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