Defining how Entamoeba histolytica nibbles vs. devours human cells

定义溶组织内阿米巴如何蚕食与吞噬人类细胞

• 批准号: 10043675
• 负责人: Katherine S Ralston
• 金额: $ 21.92万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043675
• 关键词: Abscess; Address; Amoeba genus; Bioinformatics; Biological Assay; Biology; Brain; Caenorhabditis elegans; Candidate Disease Gene; Cell Communication; Cells; Child; Data; Defect; Development; Dynamin; Embryonic Development; Entamoeba histolytica; Ephrins; Eukaryota; Genes; Genetic; Genetic Screening; Genomics; Human; Immune system; Infection; Ingestion; Intestines; Invaded; Knowledge; Large Intestine; Libraries; Literature; Liver; Lung; Lytic; Membrane; Microbe; Morbidity - disease rate; Names; Nature; Neuraxis; Organism; Pathogenesis; Phagocytosis; Phenotype; Plasmids; Play; Process; Proteins; RNA Interference; Role; Source; Tissues; Toxin; Transcriptional Regulation; Ulcer; Work; base; cell killing; deep sequencing; diarrheal disease; feeding; forward genetics; genetic selection; genome-wide; improved; innovation; knock-down; macrophage; microbial; mutant; pathogen; professional atmosphere; tool; transcriptomics

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. !

抽象的 Entamoeba Histoltica是一种原生动物病原体，是人类中的变性剂的病原体 物种名称（组织 - 组织；裂解 - 溶解）源于破坏宿主组织的能力 滋养体（“ Amoebae”）侵入大肠，导致溃疡并扩散到其他组织（例如， 肝脏，肺，大脑），导致致命的脓肿。 为了驱动组织损伤，但我们发现了一个新范式。 Amoebae通过咬住并摄入人类细胞碎片而杀死，我们将其命名为“ Amoebic Trogotictis”（Trogo-：： Nibble）（Ralston等人，自然，2014年）。 基础机制。 trogochytosis也需要吞噬作用。 Trogocytosis机制是不同的。 与吞噬作用不同。 在Trogocyposis和吞噬作用之间共享。 Trogotictis的历史记录对真核生物学具有深远的应用。 要在多细胞真核生物中使用trogotictisos进行细胞杀伤。 通信和细胞 - 细胞重塑。 因此，在开发过程中。 历史悠久的Trogotictis将在超越半径之外的广泛影响。 因为它将定义trogotictisos的机制及其与吞噬作用的不同 方法还将生成有价值的新遗传工具。 大oebiasis发病机理，广泛地针对其他感染和trogotictisosis的保守过程。 呢