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

项目摘要 宿主-微生物的相互作用是健康的关键决定因素。胃肠道提供 几种相互重叠的机制，共同起作用以防止病原体进入人体。 这些保护机制是通过肠道上皮细胞和 固有层中的免疫细胞。而专门的感官伤害性神经元检测到 病原体等有害刺激或由此造成的宿主组织损伤是已知的控制免疫的因素。 在皮肤和肺中的功能，这些神经元对肠道粘膜免疫的贡献 为人所知。 基于我们的初步数据，这个项目的总体目标是准确地确定 限制肠道细菌感染的神经免疫通讯中的伤害性感觉神经元。 这将通过选择性地消融感觉神经元，并通过实验来确定来源 SP和靶细胞(SA1)。肠道致病菌如何诱导伤害性激活 体外和体内实验(SA2)。感觉神经元免疫效应的机制认识 在肠道感染期间将达到。具体地说，伤害性感受器消融如何影响树突状细胞 将确定迁移、趋化因子的产生和黏附分子的表达(SA3)。 总之，这些拟议的研究将破译感觉性传入伤害性神经元的作用。 肠道细菌感染时对粘膜宿主的防御。

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.