Coordination of mucosal immune response to enteric bacterial pathogens by nociceptive innervation

项目摘要 宿主-微生物相互作用是健康的一个关键决定因素。胃肠道提供了 几种重叠的机制共同起作用，以防止病原体进入体内。 这些保护机制是通过协调肠上皮细胞和 固有层中的免疫细胞而专门的感觉伤害感受神经元， 已知有害刺激物如病原体或由此产生的宿主组织损伤可控制免疫应答。 虽然这些神经元在皮肤和肺中起作用，但这些神经元对肠粘膜免疫的贡献并不 知道的 根据我们的初步数据，该项目的总体目标是准确确定 限制肠道细菌感染的神经免疫通讯中的感觉伤害感受神经元。 这将通过选择性消融感觉神经元来实现，并通过实验来确定来源。 SP与靶细胞（SA 1）的免疫反应。肠道细菌病原体如何诱导大鼠的伤害性激活 体外和体内（SA 2）。感觉神经元免疫效应的机制研究 在肠道感染期间将获得。具体来说，伤害感受器消融如何影响树突状细胞 将测定迁移、趋化因子产生和粘附分子表达（SA 3）。 总之，这些拟议的研究将破译的感觉传入伤害性神经元的贡献 肠道细菌感染时的粘膜宿主防御。

Project Summary Host-microbial interactions are a critical determinant of health. The gastrointestinal tract provides several overlapping mechanisms that function together to prevent entry of pathogens into the body. These protective mechanisms are provided through the coordinated of intestinal epithelial cells and immune cells in the lamina propria. While the specialized sensory nociceptive neurons that detect noxious stimuli such as pathogens, or the resulting host tissue damage are known to control immune function in the skin and lung, the contribution of these neurons to intestinal mucosal immunity is not known. Building on our preliminary data, the overall goals of this project are to precisely determine the role of sensory nociceptive neurons in the neuro-immune communication that limits enteric bacterial infection. This will be achieved by selective ablation of sensory neurons, and experiments to determine the source of SP and the targeted cells (SA1). How an enteric bacterial pathogen induces nociceptive activation in vitro and in vivo (SA2). Mechanistic understanding of the immunological effect of sensory neurons during enteric infection will be attained. Specifically, how nociceptor ablation impinges on dendritic cell migration, chemokine production, and adhesion molecule expression will be determined (SA3). Together, these proposed studies will decipher the contribution of sensory afferent nociceptive neurons to mucosal host defense during enteric bacterial infection.