Defining how Entamoeba histolytica nibbles vs. devours human cells

摘要 溶组织内阿米巴是一种原生动物病原体，是人类阿米巴病的病原体。的 种名（histo-：组织; lytic-：溶解）来源于破坏宿主组织的能力。E. histolytica 滋养体（“阿米巴”）侵入大肠，引起溃疡并可扩散到其它组织（例如， 肝、肺、脑），导致致命的中毒。变形虫具有接触依赖性细胞杀伤活性， 导致组织损伤，但其机制尚不清楚。我们建立了一个新的范式， 变形虫通过咬下和吞噬人类细胞碎片来杀死人，我们将其命名为“变形虫胞饮症”（trogo-： 蚕食）（Ralston等人，Nature，2014）。基于这一发现，我们在这里提出描绘其 潜在机制胞啃作用可能与吞噬作用具有相同的特征，因为许多蛋白质具有 吞噬作用也是胞啃作用所必需的。然而，有迹象表明， 胞啃机制是不同的。因此，我们假设胞啃机制的各个方面是 不同于吞噬作用。我们将应用遗传学和转录组学的方法来描绘基因， 在胞啃作用和吞噬作用之间是共享的，并且对每个过程都是特异性的。超越E. trogocytica在真核生物学中具有深远的应用。几种微生物真核生物出现 利用胞啃作用杀死细胞在多细胞真核生物中，胞间刺胞作用用于细胞杀伤、细胞-细胞 通讯和细胞间重塑。胞吞作用在免疫系统、中枢神经系统、 系统和开发过程中。因此，进一步了解E. 溶组织性胞刺症将具有比阿米巴病更广泛影响。这项工作意义重大，影响巨大 因为它将定义胞啃作用的机制以及它与吞噬作用的区别。我们 这些方法还将产生有价值的新遗传工具。此外，我们的研究结果将直接适用于 阿米巴病的发病机制，并广泛地应用于其他感染和保守的胞刺过程。 !

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 its underlying mechanism. Trogocytosis is likely to share features with phagocytosis, since many proteins with roles in phagocytosis are also required for trogocytosis. However, there are emerging hints that aspects of the trogocytosis mechanism are distinct. Thus, we hypothesize that aspects of the trogocytosis mechanism are distinct from phagocytosis. We will apply genetic and transcriptomic approaches to delineate the genes that are shared between trogocytosis and phagocytosis, and those that are specific to each process. 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 have a broad impact beyond amoebiasis. This work is significant and high-impact as it will define the mechanism underlying trogocytosis and how it differs from phagocytosis. Our approaches will also generate valuable new genetic tools. Moreover, our findings will apply directly to amoebiasis pathogenesis, and broadly to other infections and the conserved process of trogocytosis. !