The role of Entamoeba histolytica trogocytosis (trogo-: nibble) in the pathogenesis of amoebiasis

摘要 溶组织内阿米巴是一种原生动物病原体，也是人类阿米巴病的病原体。这个 物种名称(组织-：组织；溶解-：溶解)源于破坏宿主组织的能力。组织裂殖吸虫 滋养体(“阿米巴”)侵入大肠，引起溃疡并可扩散到其他组织(例如， 肝、肺、脑)，导致致命的脓肿。阿米巴具有接触性细胞杀伤活性，很可能 以推动组织损伤，但其机制尚不清楚。我们建立了一个新的范式，通过发现 阿米巴虫通过咬下和吞食人类细胞碎片来杀死人，我们将其命名为阿米巴滋养细胞增多症(trogo-： 半截)(Ralston等人，《自然》，2014年)。在这一发现的基础上，我们建议在这里描绘 巨噬细胞增多症对免疫逃避的意外贡献。我们将应用成像流式细胞术，宿主和 阿米巴突变体和多种宿主细胞类型剖析巨噬细胞增多对免疫回避的贡献 在体外，我们将使用阿米巴病的小鼠模型将这些发现扩展到体内的发病机制。超越 巨噬细胞增多症在真核生物学中有着广泛的应用。几种微生物真核生物 似乎使用巨噬细胞增多症来杀死细胞。在多细胞真核生物中，巨噬细胞增多症用于杀死细胞、细胞间 沟通和细胞-细胞重塑。巨噬细胞增多症在免疫系统和中枢神经系统中发挥作用。 系统，并在开发过程中。因此，对E. 溶组织性巨噬细胞增多症将直接应用于阿米巴病的发病机制，并广泛应用于真核生物。 一般为巨噬细胞增多症。这项工作意义重大，影响巨大，因为它将为 免疫逃避和阿米巴病发病机制的一个重要方面。此外，这些研究还适用于 广义地说，巨噬细胞增多症是真核细胞-细胞相互作用的一种保守模式。 好了！

Abstract Entamoeba histolytica is a protozoan pathogen and the causative agent of amoebiasis in humans. The species name (histo-: tissue; lytic-: dissolving) derives from the ability to destroy host tissues. E. histolytica trophozoites (“amoebae”) invade the large intestine, causing ulceration and can spread to other tissues (e.g., liver, lungs, brain), causing fatal abscesses. Amoebae possess contact-dependent cell-killing activity that is likely to drive tissue damage, but the mechanism was unclear. We established a new paradigm by discovering that amoebae kill by biting off and ingesting human cell fragments, which we named “amoebic trogocytosis” (trogo-: nibble) (Ralston, et al., Nature, 2014). Building on this discovery, here we propose to delineate the unexpected contribution of trogocytosis to immune evasion. We will apply imaging flow cytometry, host and amoeba mutants, and a variety of host cell types to dissect the contribution of trogocytosis to immune avoidance in vitro, and we will use the mouse model of amoebiasis to extend these findings to pathogenesis in vivo. Beyond E. histolytica, trogocytosis has far-reaching applications to eukaryotic biology. Several microbial eukaryotes appear to use trogocytosis for cell-killing. In multicellular eukaryotes, trogocytosis is used for cell-killing, cell-cell communication and cell-cell remodeling. Trogocytosis plays roles in the immune system, in the central nervous system, and during development. Therefore, an improved understanding of the mechanism and biology of E. histolytica trogocytosis will apply both directly to the pathogenesis of amoebiasis and broadly to eukaryotic trogocytosis in general. This work is significant and high-impact as it will define a novel strategy for immune evasion and an important aspect of amoebiasis pathogenesis. Moreover, these studies apply broadly to trogocytosis as a conserved mode of eukaryotic cell-cell interaction. !