"Biting" of human cells by Entamoeba histolytica: a novel cytotoxic mechanism

描述（由申请人提供）：我提议研究阿米巴结肠炎的发病机制，阿米巴结肠炎是一种全球性寄生虫感染，是儿童发病率和死亡率的主要来源。溶组织内阿米巴因其破坏宿主组织和侵入肠道而被命名为“溶组织阿米巴”，但其机制尚不清楚。我最近有了一个惊人的发现，变形虫通过咬下并吞噬不同的人体活细胞，导致细胞内钙离子升高并最终死亡。我将其命名为“类胞刺摄取”（希腊语，trogo-：nibble），因为它与免疫细胞中的胞刺相似。我推测阿米巴结肠炎的病理是由于寄生虫通过蚕食肠道上皮细胞侵入肠道所致。很可能这部小说 杀伤机制需要独特的吞噬机制，并且这些成分代表了新的药物靶点。因此，我建议揭示的信号转导机制，类似的摄入。此外，我建议重新审视长期存在的假设，即E。被称为“阿米巴”的溶组织菌孔形成蛋白是分泌的细胞毒性效应物。这项工作的成功完成将使变形虫的功能发生范式转变，也将使我们能够识别新的毒力因子， 我们来定义疾病的基本机制。

DESCRIPTION (provided by applicant): I propose to study the pathogenesis of amoebic colitis, a global parasitic infection and a major source of morbidity and mortality of children. Entamoeba histolytica was named "histolytica" for its destruction of host tissues and invasion of the intestine, but the mechanism was unknown. I recently made the surprising discovery that amoebae kill by biting off and ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual death. I named this "trogocytosis-like ingestion" (Greek, trogo-: nibble) due to similarity to trogocytosis in immune cells. I hypothesize that pathology in amoebic colitis results from parasites invading the intestine by nibbling the epithelial cells that line the gut. It is likely that the novel killing mechanism requires unique phagocytic machinery and that the components represent new drug targets. Therefore, I propose to uncover the signaling mechanisms underlying trogocytosis-like ingestion. Furthermore, I propose to re-examine the long-standing hypothesis that the E. histolytica pore-forming proteins, known as the "amoebapores," are secreted cytotoxic effectors. Successful completion of this work will create a paradigm shift in the functio of the amoebapores, and will also allow us to identify novel virulence factors, ultimately allowing us to define the basic mechanism of disease.