Mechanism of innate immune activation by intestinal distension

肠扩张激活先天免疫的机制

• 批准号: 10458056
• 负责人: Alejandro Aballay
• 金额: $ 38.21万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10458056
• 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; Exhibits; 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; Lead; Ligands; Link; Lipopolysaccharides; Mammals; Metabolic; Microbe; Molecular; Molecular Genetics; Names; Natural Immunity; Nature; Nematoda; Nervous system structure; 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; base; beneficial microorganism; design; experimental study; fighting; formyl peptide; genetic analysis; genetic approach; immune activation; innate immune mechanisms; innate immune pathways; insight; microbial colonization; mutant; neural circuit; neuromechanism; neurotransmission; optogenetics; pathogen; pathogenic bacteria; pathogenic microbe; promoter; quorum sensing; receptor; relating to nervous system; response

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.

总结 区分有害和有益微生物的能力对于生物体的生存至关重要。增加 有证据表明，由细菌定植引起的肠道扩张激活了广泛的先天免疫， 反应我们认为，肠道微生物定植和腹胀可能被视为一种危险 激活免疫反应的信号。这种先天免疫激活依赖于输入 可以帮助识别各种微生物，并可以调节宿主 利用控制免疫稳态的神经-肠轴进行免疫反应。该提案描述了实验 旨在阐明神经系统可能感知宿主整体变化的机制， 在病原体感染期间的生理学和协调先天免疫应答。利用线虫 秀丽隐杆线虫，我们已经证明，特定的基因和神经元的神经系统中， 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能起作用， 在非神经组织上调节生物体水平的先天免疫反应。我们建议使用 各种分子和遗传技术来探索一般假设，即宿主的改变 由细菌感染引起的生理学触发针对细菌感染的先天免疫应答， 在整个动物水平上由神经系统控制。