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

描述（由申请人提供）：我拟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的寄生虫感染，也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袭肠道而被命名为“溶组织内阿米巴”，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食不同的人类活细胞片段来杀死人，导致细胞内钙含量升高，最终死亡。我将这种情况命名为“噬噬细胞样摄食”（希腊语，trogo-：啃食），因为它与免疫细胞的噬噬细胞症相似。我推测阿米巴结肠炎的病理是由于寄生虫通过啃噬肠道上皮细胞侵入肠道。很可能这本小说

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.