Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.
Nature. 2014 Apr 24;508(7497):526-30. doi: 10.1038/nature13242. Epub 2014 Apr 9.
Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named "histolytica" for its ability to destroy host tissues, which is probably driven by direct killing of human cells. The mechanism of human cell killing has been unclear, although the accepted model was that the parasites use secreted toxic effectors to kill cells before ingestion. Here we report the discovery that amoebae kill by 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 human cell fragments is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of fragments of living human cells is reminiscent of trogocytosis (from Greek trogo, nibble) observed between immune cells, but amoebic trogocytosis differs because 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 model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.
溶组织内阿米巴是阿米巴病的病原体,这是一种在发展中国家可能致命的腹泻病。该寄生虫因其破坏宿主组织的能力而被命名为“溶组织”,这可能是由直接杀死人类细胞驱动的。尽管公认的模型是寄生虫在吞噬细胞之前使用分泌的毒性效应物来杀死细胞,但人类细胞杀伤的机制尚不清楚。在这里,我们报告了一个发现,即阿米巴通过摄取活的人类细胞的不同片段来杀死细胞,导致细胞内钙升高并最终导致细胞死亡。细胞杀伤后,阿米巴会脱落并停止摄取。摄取人类细胞碎片是细胞杀伤所必需的,并且也有助于肠道组织的侵袭。活的人类细胞片段的内化让人想起免疫细胞之间观察到的 trogocytosis(来自希腊语 trogo, nibble),但阿米巴 trogocytosis 不同,因为它会导致死亡。摄取活细胞物质和排斥尸体,与多细胞生物中清除死细胞的既定模型形成鲜明对比。这些发现改变了阿米巴病中组织破坏的模型,并表明 trogocytosis 作为一种细胞间交换形式具有古老的起源。