Linking Innate and Adaptive Immunity: The Role of Eosinophils

嗜酸性粒细胞功能的公认范式是它们是先天免疫效应细胞，在防御寄生虫中发挥主要作用，并有助于过敏反应。这种模式受到了挑战的存在嗜酸性粒细胞在小肠胎儿发育期间和寄生虫感染的情况下。有证据表明，嗜酸性粒细胞在维持粘膜屏障的稳态和诱导适应性免疫应答中发挥更广泛的作用。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一致。 我们已经建立了方法，以产生单细胞悬浮液含有嗜酸性粒细胞，树突状细胞（DC），上皮细胞存在于粘膜表面的牛小肠。 使用高速细胞分选仪，我们可以分离和纯化足够数量的这些细胞群中的每一个，以进行各种各样的表型分析和功能测定。这些方法将被用来测试我们的假设，即嗜酸性粒细胞发挥了重要作用，通过直接和间接的相互作用，与粘膜上皮细胞和DC在维持肠粘膜屏障的完整性。 肠粘膜作为肠道微生物菌群和病原体的屏障以及营养物的选择性摄取部位起着双重作用。破坏这些功能中的任何一种都会威胁宿主的生命，并损害动物的健康和生产。因此，分析粘膜嗜酸性粒细胞的发育和功能将提供关于这一普遍存在的群体在调节肠内稳态中的作用的关键信息。对嗜酸性粒细胞功能的分析将有助于更好地理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抗原呈递细胞诱导保护性免疫的口服疫苗的设计和递送提供基础。

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.