Integration of Enteric Immune and Nervous Systems in the Mucosal Recall Immune Response

肠道免疫和神经系统在粘膜回忆免疫反应中的整合

• 批准号: 9335274
• 负责人: Milena Bogunovic
• 金额: $ 18.44万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-20 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9335274
• 关键词: Allergens; Anaphylaxis; Anatomy; Automobile Driving; Biology; Bronchial Spasm; Cells; Clinical; Collaborations; Communication; Complex; Data; Digestion; Eating; Embryonic Development; Enteral; Enteric Nervous System; Event; Extrinsic asthma; Failure; Food; Foundations; Future; Gastrointestinal Diseases; Gastrointestinal Physiology; Gastrointestinal tract structure; Goals; Health; Homeostasis; Hypersensitivity; Imaging Techniques; Immune; Immune response; Immune system; Individual; Infection; Inflammatory; Intestines; Knowledge; Laboratories; Link; Lymphoid Follicle; Methods; Microbe; Mucosal Immunity; Muller' s cell; Mus; National Cancer Institute; Nervous system structure; Neuroimmune; Neurons; Nociception; Pain; Parasites; Pathway interactions; Patients; Perception; Performance; Physiological; Play; Primary Infection; Process; Production; Reaction; Receptor Signaling; Reflex action; Role; Site; Smell Perception; Stimulus; System; Transgenic Mice; Vaccines; Visual; absorption; axonal guidance; bone growth factor; bone morphogenetic protein 2; bone morphogenetic protein receptors; driving force; fighting; gastrointestinal; gastrointestinal infection; improved; intravital imaging; macrophage; microbial; microbiota; mouse model; nerve supply; neuroimmunology; neurotransmission; novel; pathogen; relating to nervous system; response

PROJECT SUMMARY Gastrointestinal (GI) health is essential for overall body health, yet many gaps exist in our understanding of how GI tract is protected from infection. The GI tract is highly innervated to coordinate complex physiological responses related to food intake, digestion and absorption. Besides food, the GI tract is the entry site for microbes and parasites, but it is well protected by the local immune system. Comparison of the evolutionary and embryonic development of intestinal immune and nervous systems suggests that two systems must be integrated in their common goal to provide the best functional performance and protection of the GI tract. However, not much is known about the anatomical organization, mechanisms and driving force of neuro- immune interactions. The questions that we ask in this proposal are why and how intestinal nervous and immune systems regulate each other’s functions in response to infection. Macrophages, evolutionary most ancient immunocytes, seem to play a special role in communication with enteric neurons. We found that a specialized type of intestinal macrophages is associated with the enteric nervous system. We also observed that GI infection induces new connections between neurons and mucosal immune cells, and these connections fail to develop if macrophages are absent. We hypothesize, that remodeling of the enteric nervous system during infection is a macrophage-driven process, which results in new neuro-immune pathways of conditional “inflammatory” reflexes. By using intravital imaging and transgenic mouse approach to target functions of intestinal neurons and macrophages, we will explore the biology behind conditional inflammatory reflexes, and examine their role in the recall immune response.

项目摘要 胃肠道（GI）健康对整体身体健康至关重要，但我们对胃肠道的理解存在许多差距。 胃肠道如何免受感染胃肠道高度受神经支配，以协调复杂的生理 与食物摄入、消化和吸收有关的反应。除了食物之外，胃肠道还是 细菌和寄生虫，但它是由当地的免疫系统很好地保护。进化论的比较 肠道免疫系统和神经系统的胚胎发育表明， 它们的共同目标是提供最佳的功能性能和胃肠道保护。 然而，对神经元的解剖组织、机制和驱动力知之甚少。 免疫相互作用我们在这个建议中提出的问题是为什么以及如何肠道神经和 免疫系统在感染时相互调节功能。 巨噬细胞，进化中最古老的免疫细胞，似乎在与免疫细胞的交流中发挥着特殊的作用。 肠神经元我们发现，一种特殊类型的肠道巨噬细胞与肠道 神经系统我们还观察到，胃肠道感染诱导神经元和粘膜之间的新的连接， 免疫细胞，如果没有巨噬细胞，这些连接就无法发展。我们假设， 感染期间肠神经系统的重塑是巨噬细胞驱动的过程，其导致 条件性“炎症”反射的新神经免疫途径。通过使用活体成像和转基因 小鼠的方法来靶向肠道神经元和巨噬细胞的功能，我们将探讨背后的生物学 条件性炎症反射，并检查其在回忆免疫反应中的作用。