Mechanism of innate immune activation by intestinal distension

肠扩张激活先天免疫的机制

基本信息

批准号：
10674045
负责人：
Alejandro Aballay
金额：
--
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-22 至 2024-01-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10674045
关键词：
Ablation Afferent Neurons Animals Bacterial Infections Bacterial Toxins Behavior Behavioral C. elegans genome Caenorhabditis elegans Cells Complex Control Animal Cues Dissection Endocrine Ensure Environment Esthesia Exhibits Experimental Designs Exposure to Genes Genetic Genetic Techniques Homeostasis Host Defense Human Immune Immune response Immune signaling Immune system Infection Inflammation Inflammatory Innate Immune Response Innate Immune System Intestines Laboratories Ligands Link Lipopolysaccharides Mammals Metabolic Microbe Molecular Names Natural Immunity Nature Nematoda Nervous System Neurons Neuropeptide Y Receptor Neuropeptides Neurosecretory Systems Neurotransmitters Nociceptors Organism Pathologic Pathway interactions Physiological Physiology Play Public Health Publishing Regulation Role Signal Transduction Synapses System Technology Tissues Toxin Work avoidance behavior beneficial microorganism experimental study fighting formyl peptide genetic analysis genetic approach immune activation innate immune mechanisms innate immune pathways insight microbial colonization mutant neural neural circuit neuromechanism neurotransmission optogenetics pathogen pathogenic bacteria pathogenic microbe promoter quorum sensing receptor response

项目摘要

SUMMARY The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Increasing evidence indicates that gut distension caused by bacterial colonization activates a broad innate immune response. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. This innate immune activation depends on inputs from the intestine that can aid in the recognition of a broad range of microbes and can modulate host responses using a neural-gut axis that controls immune homeostasis. This proposal describes experiments designed to elucidate the mechanisms by which the nervous system may sense overall changes in host physiology during pathogen infections and coordinate innate immune responses. Using the nematode Caenorhabditis elegans, we have demonstrated that specific genes and neurons in the nervous system of the animal control 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. We propose the use of a variety of molecular and genetic techniques to explore the general hypothesis that alterations in host physiology caused by bacterial infections trigger innate immune responses against bacterial infections that are controlled at that whole animal level by the nervous system.

概括区分有害和有益微生物的能力对于生物的生存至关重要。增加证据表明，由细菌定植引起的肠道扩张激活了宽阔的先天免疫回复。我们建议将肠道的微生物定植和腹胀视为危险激活免疫飞行反应的信号。这种先天免疫激活取决于输入从可以帮助识别广泛微生物的肠道，可以调节宿主使用控制免疫稳态的神经态轴的反应。该建议描述了实验旨在阐明神经系统可能会感知宿主总体变化的机制病原体感染期间的生理学并协调先天免疫反应。使用线虫秀丽隐杆线虫，我们已经证明了神经系统中的特定基因和神经元动物控制免疫反应，表明来自不同神经元的细胞非自主信号可以起作用在非神经组织上调节生物水平的先天免疫反应。我们建议使用各种分子和遗传技术，以探讨宿主改变的一般假设由细菌感染引起的生理学引发了针对细菌感染的先天免疫反应通过神经系统在整个动物层面控制。