Babesia: Extracellular Vesicles and their Role in Intercellular Communication

巴贝斯虫：细胞外囊泡及其在细胞间通讯中的作用

• 批准号: 9307089
• 负责人: Cheryl Ann Lobo
• 金额: $ 21.95万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307089
• 关键词: Animals; Antibodies; Attention; Babesia; Babesiosis; Basic Science; Biological Process; Biology; Blood; Blood Transfusion; Cell Communication; Cells; Communication; Communities; Confocal Microscopy; DNA; Data; Data Set; Development; Disease; Dyes; Electron Microscopy; Environment; Erythrocytes; Event; Exercise; Face; Frequencies; Future; Gene Expression; Genes; Giemsa stain; Goals; Grant; Human; Human Biology; Image; Infection; Interruption; Intervention; Invaded; Label; Laboratories; Life; Life Cycle Stages; Measures; Mediating; Ontology; Parasitemia; Parasites; Parasitic infection; Parents; Pathogenesis; Pathway interactions; Peptides; Physiological; Population; Population Control; Proteins; Proteome; Reagent; Role; Safety; Scanning; Signal Pathway; Staining method; Stains; Stress; Structure; Technology; Time; TimeLine; Twin Multiple Birth; Vascular blood supply; Vesicle; Western Blotting; annexin A5; asexual; base; calcein AM; density; experience; extracellular; extracellular vesicles; flexibility; intercellular communication; lipophilicity; man; neglect; nutrient deprivation; success; trafficking; uptake; vesicular release

Project Abstract: Babesiosis is a zoonosis and an important blood-borne human parasitic infection. This disease has recently gained much attention because of its growing infection rate in humans by transfer from animal reservoirs; because it represents a potential threat to the blood supply; because asymptomatic infections in man are common and these can be life threatening in certain recipients. Despite the impending danger of the spread of this blood-borne infection, and the significant threat that it presents to the safety of blood transfusions, its study has been neglected. There are 4 major sub-populations of asexual parasites defined by their DNA loads (1 N; 2 N; 4N and ≥4N iRBC populations). B. divergens appears to regulate the time spent in the host RBC by building an appropriate mix of subpopulations of iRBCs that provides a high flexibility in terms of developmental options based on the proliferative needs of the population. It has become increasingly clear that most cells communicate within their immediate environment by the formation and release of extracellular vesicles (ECVs). Extracellular vesicles derived from ``donor parasitized cells'' can have profound effects on ``recipient cells'' by altering gene expression and modulating signaling pathways resulting in developmental changes. We have identified extracellular vesicles (ECVs) that are released from babesia iRBCs and hypothesize that these ECVs are the mode of communication between infected RCS, leading to the choice of a specific developmental pathway. We will explore this hypothesis by (1) characterizing the repertoire of ECVs released by B. divergens under various physiological conditions and (2) establish whether specific populations of ECVs function in cell-cell communication. By focusing on those intended for extracellular trafficking, we may identify means of intercellular communication that will be analyzed in future studies. Success is predicted by our experience with Babesia biology, robust preliminary data, cutting edge technology and having all necessary reagents in place to perform the studies. This R21 grant will provide an important dataset to the parasite community and provide further evidence of the role of ECVs in parasite pathogenesis.

项目摘要： 巴贝斯虫病是一种人畜共患病，是一种重要的血源性人类寄生虫感染。这种病 由于其通过转移在人类中的感染率不断上升，最近引起了广泛关注 来自动物宿主；因为它对血液供应构成潜在威胁；因为 无症状感染在人类中很常见，在某些情况下可能会危及生命 收件人。尽管这种血源性感染传播的危险迫在眉睫，而且 它对输血安全构成重大威胁，其研究已 被忽视了。无性寄生虫有 4 个主要亚群，根据其 DNA 载量定义 （1 N；2 N；4N 和≥4N iRBC 群体）。 B. divergens 似乎可以调节花在 通过构建 iRBC 亚群的适当组合来宿主 RBC，从而提供高 基于人口激增需求的发展选择具有灵活性。它 越来越清楚的是，大多数细胞在其直接环境中进行交流 通过细胞外囊泡（ECV）的形成和释放。细胞外囊泡来源 来自“供体寄生细胞”的病毒可以通过改变基因对“受体细胞”产生深远的影响 表达和调节信号通路导致发育变化。我们有 鉴定出巴贝虫 iRBC 释放的细胞外囊泡 (ECV) 并假设 这些 ECV 是受感染 RCS 之间的通信模式，从而导致 选择特定的发展路径。我们将通过（1）来探讨这个假设 表征不同生理条件下 B. divergens 释放的 ECV 库 (2) 确定特定的 ECV 群体是否在细胞间发挥作用 沟通。通过关注那些用于细胞外贩运的物质，我们可以确定 细胞间通讯的方式将在未来的研究中进行分析。成功是 根据我们在巴贝虫生物学方面的经验、可靠的初步数据、尖端技术预测 技术并拥有进行研究所需的所有必要试剂。这项 R21 补助金 将为寄生虫界提供重要的数据集，并提供进一步的证据 ECV 在寄生虫发病机制中的作用。