Mechanisms of signaling between the nervous and immune systems.

神经系统和免疫系统之间的信号传导机制。

• 批准号: 10599242
• 负责人: Lydia Johanna Borjon
• 金额: $ 7.38万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599242
• 关键词: Action Potentials; Adult; Affect; Animals; Asthma; Axon; Back; Behavior; Behavioral; Biological Models; Brain; Cells; Chemicals; Colitis; Communication; Complex Regional Pain Syndromes; Data; Dendrites; Disease; Drosophila genus; Drosophila melanogaster; Electron Microscopy; Encapsulated; Ensure; Feedback; Female; Fibromyalgia; Functional Imaging; Future; Genes; Genetic; Goals; Hemocytes; Hemolymph; Human; Immune; Immune response; Immune signaling; Immune system; Immunity; Immunology; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Knock-out; Larva; Link; Mammals; Mechanics; Molecular; Natural Immunity; Nervous System; Neurobiology; Neurogenic Inflammation; Neuroglia; Neuroimmune; Neurons; Nociception; Nociceptors; Organism; Output; Pain; Participant; Pathologic; Pathway interactions; Peripheral; Play; Population; Proliferating; Psoriasis; Publishing; Recruitment Activity; Research; Rheumatoid Arthritis; Role; Screening Result; Signal Transduction; Site; Stereotyping; Stimulus; Synapses; System; Testing; Therapeutic Intervention; Vesicle; Wasps; Work; cell type; chronic pain; chronic pain management; egg; fluorescence imaging; genetic approach; immune activation; improved; loss of function; lymph nodes; mechanical force; microscopic imaging; neuroinflammation; optogenetics; pain sensation; prevent; receptor; response; tool; transmission blocking; transmission process; vesicular release; wound; wound healing

PROJECT SUMMARY/ABSTRACT Pain sensation (nociception) and immunity work together to protect animals from injury and infection. The nervous system and immune system are typically studied separately in their own subfields, however understanding the link between them is critical for the treatment of chronic pain and inflammatory diseases. This proposal bridges these fields to understand how neurons communicate with immune cells in the Drosophila model system. In Drosophila larvae, nociception is characterized by a stereotyped rolling behavior, triggered by several types of noxious stimuli, such as heat, chemicals, and mechanical force. The neurons that sense noxious input (nociceptors) tile each segment of the larval body wall. A population of hemocytes reside near peripheral neuron dendrites. After a noxious challenge, these hemocytes divide and differentiate into mature immune cells which then circulate in the hemolymph to find and encapsulate wounds and foreign invaders. Nociceptor activity is necessary for the initiation of a robust immune response, suggesting that noxious information is transmitted to hemocytes when a threat is perceived. The main hypothesis tested in this proposal is that nociceptors communicate with hemocytes through signaling at nociceptor dendrites. Neurogenic immune activation in mammals occurs through a mechanism of backwards propagating action potentials that trigger the release of proinflammatory factors from peripheral terminals. Using the precise genetic tools available in Drosophila, I aim to investigate the mechanisms of signaling between larval nociceptors and immune cells. I will investigate whether both central and peripheral nociceptive pathways contribute to neurogenic immune responses (Aim 1), and whether neuro-immune signaling involves backwards propagating action potentials and dendritic vesicle release, similar to mechanisms of neurogenic inflammation in mammals (Aim 2). A long-term goal is to use this system to identify additional molecular participants in neuro-immune communication through a nociceptor-specific screen (Future Aim 3). Results from this project will further our understanding of the proinflammatory role of nociceptors, and the mechanisms by which nociceptors induce immune responses. This will have important implications for our understanding and treatment of chronic pain and inflammatory conditions, while also elucidating general neurobiological principles that are not well understood, such as dendritic vesicle release and non-canonical action potential propagation.

项目摘要/摘要 疼痛感（伤害感受）和免疫力共同保护动物免受伤害和感染。这 神经系统和免疫系统通常在自己的子场中分别研究 了解它们之间的联系对于治疗慢性疼痛和炎症性疾病至关重要。这 提案桥接这些领域，以了解神经元如何与果蝇中的免疫细胞通信 模型系统。 在果蝇幼虫中，伤害感受的特征是刻板的滚动行为，由几个触发 有害刺激的类型，例如热，化学物质和机械力。感觉有害输入的神经元 （伤害感受器）瓷砖幼虫体壁的每个段。一群血细胞居住在周围神经元附近 树突。经过有害的挑战，这些血细胞分裂并分化为成熟的免疫细胞 然后在血淋巴中循环以发现并封装伤口和外国入侵者。伤害感受器的活动是 启动强大的免疫反应所必需的，这表明有害信息传递到 当感知威胁时，血细胞。 该提案中检验的主要假设是伤害感受器与血细胞进行交流 通过在伤害感受器树突处进行信号传导。哺乳动物中的神经源性免疫激活发生 向后传播动作电位的机理，从而触发促炎因子的释放 外围终端。使用果蝇中可用的精确遗传工具，我旨在调查机制 幼虫伤害感受器和免疫细胞之间的信号传导。我将调查中央和外围是否 伤害性途径有助于神经源性免疫反应（AIM 1），以及神经免疫信号是否传导 涉及向后传播动作电位和树突囊泡释放，类似于机制 哺乳动物的神经源性炎症（AIM 2）。一个长期目标是使用该系统来识别其他 通过伤害感受器特异性屏幕进行神经免疫通信的分子参与者（Future Aim 3）。 该项目的结果将进一步了解伤害感受器的促炎作用，以及 伤害感受器诱导免疫反应的机制。这将对我们的重要意义 了解和治疗慢性疼痛和炎症状况，同时阐明一般 神经生物学原理尚不清楚，例如树突囊泡释放和非典型 动作潜力传播。