Innate Immune Defense Mechanisms in the Intestine

肠道的先天免疫防御机制

基本信息

批准号：
10532754
负责人：
HANS-CHRISTIAN REINECKER
金额：
$ 69.62万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10532754
关键词：
Acetylation Actins Affinity Amino Acid Motifs Binding Biological Models Bone Marrow Cells Chimera organism Complex Cytoskeleton Deacetylation Defense Mechanisms Detection Epithelial Cells Epithelium Event Family member Genetic Genetic Transcription Goals HDAC6 gene Host Defense Host Defense Mechanism Human Immune Immune response Immune signaling Immunity Infection Innate Immune Response Intestines Listeria monocytogenes Macrophage Mediating Microtubule Stabilization Microtubule stabilizing agent Microtubules Monitor Monoclonal Antibodies Mus Myelogenous Natural Immunity Outcome Pathway interactions Pattern Recognition Pattern recognition receptor Peptides Peptidoglycan Phenotype Phosphorylation Positioning Attribute Protein Dephosphorylation Proteome Reporter Research Design Role Signal Transduction Specific qualifier value System T-Lymphocyte Variant adaptive immune response adaptive immunity antimicrobial cell type coping defense response experimental group experimental study immune activation inhibitor innate immune pathways intestinal epithelium microbial pathogen peptidoglycan receptor programs receptor response single-cell RNA sequencing three-dimensional modeling transcriptome sequencing uptake

项目摘要

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.

项目摘要 GEF-H1-IKKε-IRF5信号传导轴是识别的必要途径肽聚糖并实现宿主的防御反应，以应对细胞内病原体，例如单核细胞增生李斯特菌。巨噬细胞包含一个无活跃的GEF-H1的储层通过去磷酸化激活以形成信号平台以控制的微管先天和适应性免疫。 GEF-H1途径的位置很好，可以允许细胞内检测细胞侵入性病原体。由于许多病原体已经开发了机制细胞内存活和免疫避免，GEF-H1途径可能已经发展为靶向细胞骨架成分的微生物作用的临界免疫检测。但是，它尚不清楚微生物效应和模式识别受体如何调节微管激活GEF-H1的动力学。该应用程序寻求支持旨在的研究了解GEF-H1在微生物检测中的关键作用并定义精度要求通过基于微管的微生物模式识别激活免疫反应。