Mucosal T cell response to oral infection

粘膜免疫系统经常暴露于各种各样的粘膜， 病原微生物种类。这种慢性暴露于炎症介质和非致病性 生物体使得产生适当的免疫应答对于维持 消除有害病原体和调节对非病原生物的反应。虽然李斯特菌 单核细胞增多症（LM）（B类生物防御优先病原体）是最广泛使用的病原体之一 病原体检查T细胞免疫应答，很少有人知道诱导粘膜CDS T细胞 口腔感染后的反应待检验的总体假设是效应CD8 T细胞亚群是 差异调节粘膜环境线索，以促进快速的局部保护。我们会解决这个问题 使用更接近模拟人类感染的新的口腔感染模型的假设。具体目标 该项目的主要内容是： 目的1：确定导致保护性粘膜CDS T细胞记忆产生的解剖学事件。 目的2：了解CDS T细胞启动响应口腔细菌感染的动态变化。 目的3：探讨保护性黏膜CDS记忆T细胞发育的调控机制。 这项研究将检查CDS T细胞通过记忆T细胞分化的最早事件。 内稳态和对第二次激发的回忆。检查效应T细胞的诱导和免疫应答。 维持和回忆记忆T细胞对真正的肠道病原体，密切模仿人类感染， 这对于更好地理解肠粘膜中CDS T细胞免疫至关重要。获得的知识 从这个建议有广泛的应用潜力，从了解免疫反应， 肠道病原体到粘膜疫苗设计。 相关性（参见说明）： 这个项目将定义控制肠道细菌感染的免疫反应的参数 通过摄入病原体传播所用的小鼠模型重现了人类感染， 因此与理解粘膜免疫和疫苗接种有直接关系。

The mucosal immune system is constantly exposed to a wide range of commensal and potentially pathogenic microbial species. This chronic exposure to inflammatory mediators and nonpathogenic organisms makes generation of an appropriate immune response critical in maintaining a balance between elimination of harmful pathogens and regulating responses to nonpathogenic organisms. While Listeria monocytogenes (LM) (a category B Biodefense priority pathogen) is one of the most widely utilized pathogens for examining T cell immune responses, little is known about induction of the mucosal CDS T cell response after oral infection. The overall hypothesis to be tested is that effector CDS T cell subsets are differentially regulated by mucosal environmental cues to promote rapid local protection. We will address this hypothesis using a new oral infection model that more closely mimics the human infection. The specific aims of the project are: Aim 1: To define the anatomical events leading to generation of protective mucosal CDS T cell memory. Aim 2: To understand the dynamics of CDS T cell priming in response to oral bacterial infection. Aim 3: To define the mechanisms regulating development of protective mucosal CDS memory T cells. The studies proposed will examine the eariiest events of CDS T cell differentiation through memory T cell homeostasis and recall to secondary challenge. Examining the induction of effector T cells and the maintenance and recall of memory T cells to a bona fide gut pathogen that closely mimics human infection is critical for a better understanding of CDS T cell immunity in the intestinal mucosa. The knowledge gained from this proposal has broad application potential ranging from understanding the immune response to intestinal pathogens to mucosal vaccine designs. RELEVANCE (See instructions): This project will define the parameters controlling the immune response to an intestinal bacterial infection transmitted through ingestion of the pathogen. The mouse model used recapitulates the human infection and therefore has direct relevance to understanding mucosal immunity and vaccination.