Babesia: Extracellular Vesicles and their Role in Intercellular Communication

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病。这种病 最近，由于其通过传播在人类中的感染率不断上升，它受到了极大的关注 来自动物蓄水池；因为它对血液供应构成潜在威胁；因为 无症状感染在男性中很常见，在某些情况下可能危及生命 收件人。尽管这种血液传播感染的危险迫在眉睫，而且 它对输血安全构成了重大威胁，它的研究一直在进行 被忽视了。根据DNA载量，无性寄生虫有4个主要亚群 (1个N；2个N；4N和≥4N个红血球种群)。B.发散性似乎调节了在 通过构建适当的iRBC亚群组合来承载RBC，从而提供高 根据人口不断增长的需要，在发展选择方面的灵活性。它 已经变得越来越清楚，大多数细胞在其邻近的环境中进行通信 通过细胞外小泡(ECV)的形成和释放。来源于细胞外的囊泡 来自“供体寄生细胞”的基因可以通过改变基因对“受体细胞”产生深远影响 表达和调节信号通路导致发育变化。我们有 巴贝斯虫iRBC释放的细胞外小泡(ECV)的鉴定和假说 这些ECV是受感染的RC之间的通信模式，导致 选择一条特定的发育途径。我们将通过(1)来探讨这一假设 分枝杆菌在不同生理条件下释放的ECV的特性 条件和(2)确定特定的ECV群体是否在细胞-细胞中起作用 沟通。通过关注那些旨在进行细胞外贩运的分子，我们可能会发现 将在未来的研究中分析的细胞间通信方式。成功就是 根据我们对巴贝西亚生物学的经验预测，稳健的初步数据，尖端 技术，并拥有进行研究所需的所有试剂。这笔R21拨款 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在寄生虫致病中的作用。

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.