Linking Innate and Adaptive Immunity: The Role of Eosinophils

连接先天免疫和适应性免疫：嗜酸性粒细胞的作用

• 批准号: 250184-2013
• 负责人: Griebel, Philip
• 金额: $ 2.87万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570838
• 关键词: Linking; Innate; Adaptive; Immunity; Role

The accepted paradigm for eosinophil function is that they are innate immune effector cells that play a primary role in defence against parasites and contribute to allergic reactions. This paradigm has been challenged by the presence of eosinophils in the small intestine during fetal development and in the absence of parasitic infections. Evidence is emerging that eosinophils play a much broader role in maintaining the homoestasis of mucosal barriers and the induction of adaptive immune responses. These concepts are consistent with the capacity of eosinophils to release a wide variety of cytokines, chemokines, and pro-inflammatory mediators. We have established the methodology to generate single cell suspensions containing the eosinophils, dendritic cells (DCs), and epithelial cells present at the mucosal surface of the bovine small intestine. With a highspeed cell sorter we can isolate and purify each of these cell populations in sufficient numbers to perform a wide variety of phenotype analysis and function assays. These methodologies will be used to test our hypothesis that eosinophils play a significant role in maintaining the integrity of the intestinal mucosal barrier through direct and indirect interactions with both mucosal epithelial cells and DCs. The intestinal mucosa plays a dual role as a barrier to commensal microflora and pathogens and a site for the selective uptake of nutrients. Disrupting either of these functions threatens the life of the host and compromises health and production in animals. Therefore, analyzing mucosal eosinophil development and function will provide critical information regarding the role(s) of this ubiquitous population in regulating intestinal homeostasis. The analysis of eosinophil function will provide a greater understanding of the pathogenesis of enteric infections and the mechanisms that determine the balance between immune protection and immune pathology.This knowledge will also provide the basis for the design and delivery of oral vaccines that effectively target the antigen presenting cells capable of inducing protective immunity.

公认的嗜酸性粒细胞功能的范例是，它们是先天免疫效应细胞，在防御寄生虫和促进过敏反应中发挥主要作用。在胎儿发育过程中和没有寄生虫感染的情况下，小肠中存在嗜酸性粒细胞，这一模式受到了挑战。越来越多的证据表明，嗜酸性粒细胞在维持粘膜屏障的同质性和诱导适应性免疫反应方面发挥着更广泛的作用。这些概念与嗜酸性粒细胞释放多种细胞因子、趋化因子和促炎介质的能力是一致的。 我们已经建立了产生单细胞悬液的方法，其中包含存在于牛小肠粘膜表面的嗜酸性粒细胞、树突状细胞(DC)和上皮细胞。有了高速细胞分选机，我们可以分离和纯化足够数量的每一个细胞群，以执行各种表型分析和功能分析。这些方法将被用来检验我们的假设，即嗜酸性粒细胞通过与粘膜上皮细胞和DC直接和间接相互作用，在维持肠粘膜屏障的完整性方面发挥重要作用。 肠粘膜既是共生微生物和病原体的屏障，又是营养物质选择性吸收的场所。扰乱这些功能中的任何一种都会威胁宿主的生命，并危及动物的健康和生产。因此，分析粘膜嗜酸性粒细胞的发育和功能将提供有关这一无处不在的人群在调节肠道内环境平衡中所扮演的角色(S)的关键信息。对嗜酸性粒细胞功能的分析将有助于更好地了解肠道感染的发病机制，以及决定免疫保护和免疫病理之间平衡的机制。这些知识也将为有效靶向能够诱导保护性免疫的抗原提呈细胞的口服疫苗的设计和交付提供基础。