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兽共患传染病，是人体重要的血液传播寄生虫病。这种疾病 由于其通过转移在人类中的感染率越来越高， 从动物水库;因为它代表了一个潜在的威胁，血液供应;因为 男性无症状感染很常见，在某些情况下可能危及生命。 受惠人士尽管这种血液传播感染的传播危险迫在眉睫， 它对输血安全性构成重大威胁，其研究已被 忽视根据DNA载量，无性生殖寄生虫有4个主要亚群 （1 N; 2 N; 4 N和≥ 4 N iRBC群体）。B。分歧者似乎调节了花在 通过构建适当的iRBC亚群混合物， 根据人口增长的需要，在发展选择方面具有灵活性。它 越来越清楚的是，大多数细胞在其直接环境中进行通信， 通过细胞外囊泡（ECV）的形成和释放。细胞外囊泡 “供体寄生细胞”的基因突变可以通过改变基因对“受体细胞”产生深远的影响， 表达和调节导致发育变化的信号通路。我们有 鉴定了从婴儿红细胞释放的细胞外囊泡（ECV），并假设 这些ECV是受感染的RCS之间的通信模式，导致 选择特定的发展道路。我们将通过（1）来探讨这个假设。 表征由B释放的ECV的库。在各种生理条件下， 条件和（2）确定ECV的特定群体是否在细胞-细胞间功能 通信通过关注那些打算用于细胞外运输的，我们可以确定 细胞间通讯的手段，将在未来的研究中进行分析。成功是 根据我们在Babybird生物学方面的经验，可靠的初步数据，尖端的 技术和所有必要的试剂到位进行研究。R21补助金 将为寄生虫群落提供重要的数据集，并提供进一步的证据， ECV在寄生虫发病机制中的作用。