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，在防御寄生虫和促进过敏反应中起主要作用。在胎儿发育期间小肠中嗜酸性粒细胞的存在和没有寄生虫感染的情况下，这一范式受到了挑战。越来越多的证据表明，嗜酸性粒细胞在维持粘膜屏障的内平衡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。我们已经建立了一种方法来产生含有嗜酸性粒细胞、树突状细胞（dc）和存在于牛小肠粘膜表面的上皮细胞的单细胞悬浮液。使用高速细胞分选器，我们可以分离和纯化足够数量的这些细胞群，以执行各种各样的表型分析和功能分析。这些方法将用于验证我们的假设，即嗜酸性粒细胞通过与粘膜上皮细胞和dc的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。肠道黏膜具有双重作用，既是共生菌群和病原体的屏障，又是营养物质选择性吸收的场所。破坏这些功能中的任何一种都会威胁到宿主的生命，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为这一普遍存在的群体在调节肠道稳态中的作用提供关键信息。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。这一知识也将为设计和提供口服疫苗提供基础，这些疫苗可以有效地靶向能够诱导保护性免疫的抗原提呈细胞。

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.