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

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

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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.

项目摘要炎症是一种进化保守的反应，对健康有益和有害影响。过度和延长的炎症反应会促进对宿主组织的损害，并有助于许多慢性人类疾病，而炎症不足会促进感染的敏感性。仍然是尚不清楚如何确定这些亲和抗炎因素的平衡，因此为什么炎症在某些情况下，持续存在并变得慢性，而不是其他情况。由于炎症的抗菌作用，微生物已经发展了干扰炎症反应的策略。我们出版和初步研究提供了证据，表明分泌的李斯特菌单核细胞增生（LM）促毒力促进蛋白（p60）特别针对树突状细胞的CDC1子集，以促进NK细胞的IL-10产生。 IL-10是a 细胞因子对于解决炎症很重要。我们提出的研究将剖析a的机制 p60中存在的特定结构域以及来自许多其他细菌的蛋白质引起了这种反应。具体而言，我们研究了新鉴定的受体如何促进对p60的反应，p60如何起作用一次 p60的细胞和独特的特征，这些特征支持其操纵免疫反应的能力。