Innate Immune Defense Mechanisms in the Intestine

项目摘要 ε-IRF5信号转导通路是细胞周期调控的重要途径 并使宿主防御反应能够应对细胞内的病原体，如 单核细胞增多性李斯特菌巨噬细胞含有结合在一起的不活跃的环境基金-H1 通过去磷酸化激活的微管，形成信号平台，控制 先天免疫和获得性免疫。全球环境基金-H1途径处于有利地位，使细胞内 细胞侵袭性病原体的检测。因为许多病原体已经发展出一种机制 细胞内的生存和免疫回避，环境基金-H1途径可能已经进化到允许 针对细胞骨架组件的微生物效应器的关键免疫检测。然而，它 目前尚不清楚微生物效应器和模式识别受体如何调节微管 全球环境基金-H1的激活动力学。此应用程序寻求对旨在 了解全球环境基金-H1在微生物检测中的关键作用，并确定准确的要求 用于通过基于微管的微生物模式识别来激活免疫反应。

Project Summary The GEF-H1-IKKε-IRF5 signaling axis is an essential pathway for the recognition of peptidoglycans and enables host defense responses to cope with intracellular pathogens such as Listeria monocytogenes. Macrophages contain a reservoir of inactive GEF-H1 bound to microtubules that is activated by dephosphorylation to form signaling platforms for the control of innate and adaptive immunity. The GEF-H1 pathway is well positioned to allow the intracellular detection of cell-invasive pathogens. As many pathogens have developed mechanisms for intracellular survival and immune avoidance, the GEF-H1 pathway may have evolved to allow critical immune detection of microbial effectors that target cytoskeletal components. However, it is unclear how microbial effectors and pattern recognition receptors regulate microtubule dynamics for the activation of GEF-H1. This application seeks support for studies designed to understand the key role of GEF-H1 in microbial detection and to define the precise requirements for the activation of immune responses through microtubule based microbial pattern recognition.