Genetic analysis of innate immunity using C. elegans

使用秀丽隐杆线虫进行先天免疫的遗传分析

基本信息

批准号：
9593433
负责人：
Alejandro Aballay
金额：
$ 31.53万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9593433
关键词：
Ablation Adrenergic Agents American Society of Hematology Animals Bacterial Infections C. elegans genome Caenorhabditis elegans Calcium Cells Characteristics Collaborations Communication Disease Dissection Dopamine Receptor Endocrine Environment G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs Genes Genetic Techniques Homeostasis Host Defense Immune Immune response Immune system Infection Inflammation Innate Immune Response Innate Immune System Lead Ligands Link MAP Kinase Gene MAPK14 gene Mammals Mediator of activation protein Metabolic Microbe Molecular Molecular Genetics Monitor Natural Immunity Nature Nematoda Nervous System control Nervous system structure Neurons Neuropeptide Y Receptor Neuropeptides Neurosecretory Systems Neurotransmitters Organism Pathologic Pathway interactions Pattern Pharmaceutical Preparations Physiological Physiological Processes Predisposition Probiotics Process Proteins Publishing Regulation Role Signal Transduction Signaling Molecule Stimulus Surface Synapses System Technology Tissues design experimental study genetic analysis genetic approach immune activation immune function immunoregulation insight killings microbial microbicide millisecond mutant neural circuit neuromechanism new therapeutic target octopamine receptor optogenetics pathogen pathogen exposure prevent protein folding receptor receptor-mediated signaling relating to nervous system response sensor

项目摘要

SUMMARY The innate immune system is the front line of host defense against microbial infections, but its rapid and uncontrolled activation elicits microbicidal mechanisms that have deleterious effects. Increasing evidence indicates that the metazoan nervous system, which responds to stimuli originating from both the internal and the external environment, functions as a modulatory apparatus that controls not only microbial killing pathways but also cellular homeostatic mechanisms. However, given the complexity of the nervous and immune systems of mammals, the precise mechanisms by which the two systems influence one another remain understudied. This proposal describes experiments designed to elucidate the mechanism by which the nervous system may sense pathogens and/or probiotic microbe-associated molecular patterns (MAMPs) and control innate immunity. Using the nematode Caenorhabditis elegans, we have recently demonstrated that G-protein coupled receptor (GPCR) signaling in at least 9 different neurons controls immune responses, indicating that cell non- autonomous signals from different neurons may act on non-neural tissues to regulate innate immune responses at the organismal level. GPCR signaling in the aforementioned neurons controls microbial killing pathways and a conserved unfolded protein response pathway that may be necessary to alleviate the increased demand on protein folding during immune activation. In this proposal, we will use a variety of molecular and genetic techniques to explore the general hypothesis that the nervous system regulates immune homeostasis during the host response to pathogen infections at the whole animal level.

概括先天免疫系统是宿主防御微生物感染的前线，但它的迅速和不受控制的激活会引起具有有害作用的微生物机制。越来越多的证据表明对内部和内部和外部环境，作为一种调节设备，不仅控制微生物杀戮途径还有细胞稳态机制。但是，鉴于神经和免疫系统的复杂性在哺乳动物中，两个系统互相影响的确切机制仍在研究中。该建议描述了旨在阐明神经系统可能的机制的实验感官病原体和/或益生菌微生物相关的分子模式（MAMP）和控制先天免疫。使用线虫秀丽隐杆线虫，我们最近证明了G蛋白耦合至少9种不同神经元中的受体（GPCR）信号传导控制免疫反应，表明细胞非 - 来自不同神经元的自主信号可能作用于非神经组织以调节先天免疫有机层的反应。上述神经元中的GPCR信号传导控制微生物杀伤途径和保守的展开的蛋白质反应途径可能是减轻所必需的免疫激活期间对蛋白质折叠的需求增加。在此提案中，我们将使用各种分子和遗传技术探讨神经系统调节免疫的一般假设宿主对整个动物水平的病原体感染的反应中的稳态。