Dendritic cell targeting by bacterial LysM proteins to suppress inflammation

树突状细胞通过细菌 LysM 蛋白靶向抑制炎症

基本信息

批准号：
10750594
负责人：
Laurel L Lenz
金额：
$ 46.38万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750594
关键词：
Activated Natural Killer Cell Amino Acids Animals Anti-Bacterial Agents Anti-Inflammatory Agents Antigens Antimicrobial Effect Arthritis Atherosclerosis Attenuated Automobile Driving Bacteria Bacterial Infections Bacterial Proteins Binding Bone Marrow Cells Chronic Chronic Obstructive Pulmonary Disease Cross Presentation Data Dendritic Cells Development Endocytosis Endosomes Equilibrium Health ICAM1 gene Immune response Infection Inflammation Inflammatory Inflammatory Response Interferon Type II Interleukin-10 Invaded Lipids Listeria monocytogenes Lung Lymphocyte Malignant Neoplasms Mediating Membrane Proteins Microbe Mitochondria Mitochondrial Proteins Myeloid Cells NK Cell Activation Natural Killer Cells Organism Pathogenicity Pathway interactions Phenotype Play Polysaccharides Predisposition Production Proteins Proteomics Publishing Reaction Recombinants Resolution Role Route Shapes Streptococcus pneumoniae Surface Tertiary Protein Structure Testing Tissues Virulence Work crosslink cytokine human disease microbial pathogen pathogenic bacteria polypeptide receptor release factor response tumor

项目摘要

Project Summary Inflammation is an evolutionarily conserved reaction with both beneficial and detrimental impacts on health. Excessive and prolonged inflammatory responses can promote damage to host tissues and contribute to numerous chronic human diseases while inadequate inflammation promotes susceptibility to infection. It is still not clear how the balance of these pro-and anti-inflammatory factors is determined and thus why inflammation persists and becomes chronic in some contexts, but not others. Due to the antimicrobial effects of inflammation, microbes have evolved strategies to interfere with the inflammatory response. Our published and preliminary studies have provided evidence that a secreted Listeria monocytogenes (Lm) virulence-promoting protein (p60) specifically targets the cDC1 subset of dendritic cells to promote the production of IL-10 by NK cells. IL-10 is a cytokine important for resolution of inflammation. Our proposed studies will dissect the mechanisms by which a specific domain present in p60 as well as proteins from numerous other bacteria acts to induce this response. Specifically, we investigate how newly identified receptors promote the response to p60, how p60 acts once in the cell, and unique features of p60 that support it ability to manipulate immune responses.

项目概要炎症是一种进化上保守的反应，对健康既有有益的影响，也有有害的影响。过度和长期的炎症反应会促进宿主组织的损伤并导致多种慢性人类疾病，而炎症不足会增加感染的易感性。依然是不清楚这些促炎因子和抗炎因子的平衡是如何确定的以及为什么会发生炎症在某些情况下会持续存在并变成慢性，但在其他情况下则不会。由于炎症的抗菌作用，微生物已经进化出干扰炎症反应的策略。我们已发布的和初步的研究提供证据表明，分泌型单核细胞增生李斯特菌 (Lm) 毒力促进蛋白 (p60) 专门针对树突状细胞的 CDC1 子集，以促进 NK 细胞产生 IL-10。 IL-10 是一种细胞因子对于炎症的消退很重要。我们提出的研究将剖析一个机制 p60 中存在的特定结构域以及来自许多其他细菌的蛋白质可诱导这种反应。具体来说，我们研究了新发现的受体如何促进对 p60 的反应，p60 在体内如何发挥作用。细胞以及 p60 的独特特征支持其操纵免疫反应的能力。