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

溶组织内阿米巴 trogocytosis（trogo-：nibble）在阿米巴病发病机制中的作用

基本信息

批准号：
10404102
负责人：
Katherine S Ralston
金额：
$ 17.67万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10404102
关键词：
Abscess Actins Address Amoeba genus Animal Model Animals Biology Blood Brain Cell Communication Cell Membrane Proteins Cells Chemotaxis Child Complement Cytochalasin D Cytolysis Defect Development Dual-role transvestism Entamoeba histolytica Eukaryota Eukaryotic Cell Flow Cytometry Human Image Immune Immune Evasion Immune system In Vitro Ingestion Intestines Invaded Knowledge Large Intestine Liver Lung Lytic Mediating Membrane Proteins Microbe Modeling Morbidity - disease rate Mus Names Nature Neuraxis Pathogenesis Phagocytosis Play Principal Investigator Proteins Proteomics Resistance Role Serum Source Surface Testing Tissues Ulcer Work animal imaging cell killing cell type diarrheal disease genetic regulatory protein improved in vivo innovation microbial mouse model mutant neutrophil novel strategies pathogen professional atmosphere

项目摘要

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. !

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）。 trogocytosis对免疫电子的意外贡献。变形虫突变体和各种宿主细胞类型，以显示Trogotictis对免疫避免的贡献在体外，我们将使用小鼠模型将这些发现扩展到体内病原体 E. histoltica，Trogocytosis对真核生物学的应用众多。似乎在多细胞真核生物中使用trogocyocyposis。通信和细胞 - 细胞重塑。因此，在开发过程中。溶组织trogococytosis均直接适用于大oebiasis的病原体，并广泛地对真核生物一般免疫逃避和阿米巴病的重要方面，这些研究适用广泛地呈trogocytosis，就像真核细胞 - 细胞相互作用的保守模式一样。呢