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

• 批准号: 10676724
• 负责人: Alejandro Aballay
• 金额: $ 2.6万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10676724
• 关键词: Animals; Caenorhabditis elegans; Communication; Cues; Disease; Endocrine; Genes; Goals; Immune; Immune response; Immune system; Immunity; Immunologic Memory; Infection; Inflammation; Innate Immune Response; Innate Immune System; Instruction; Intestines; Mammals; Metabolic; Natural Immunity; Nematoda; Nervous System; Neurons; Neurosecretory Systems; Neurotransmitters; Pathogenicity; Pathologic; Pathway interactions; Physiological; Physiology; Play; Regulation; Role; Signal Transduction; Site; Tissues; Travel; communication behavior; genetic analysis; genetic approach; gut colonization; immune activation; immunoregulation; microbiota; neural; neural circuit; new therapeutic target; next generation; pathogen; pathogen exposure; pathogenic bacteria; response; transmission process

Increasing evidence suggests that the intestine plays an important role in sensing not only the presence of pathogens but also changes in the microbiota, which ultimately result in changes in the regulation of immune pathways and behaviors by communicating with neurons. However, the complexity of the nervous and immune systems of mammals makes it difficult to dissect the mechanisms by which the neural-gut axis communicates using bidirectional signals to control intestinal immunity. Studies in the nematode Caenorhabditis elegans show that bacterial colonization of the intestine results in the activation of the expression of innate immune genes in the gut and the activation of a neuroendocrine signal that controls pathogen avoidance. The germline also plays a key role in the neural-gut axis not only by transmitting the immunological memory to the next generation but also by communicating pathogenic cues that travel from the gut to the nervous system to control innate immunity. The long-term goal of this proposal is to elucidate the mechanism by which the neural-germline-gut axis communicates to sense pathogens and/or infection-induced physiological changes to control innate immunity at the whole animal level. Thus, we will explore the general hypothesis that the neural-germline-gut axis plays a critical role in the organismal response against bacterial pathogens by helping the nervous system integrate signals from infected sites and different tissues to coordinate the immune response. Specific genes and neurons will be studied to dissect the neural circuits that regulate immune activation in response to pathogen exposure and pathogen-induced alterations of the animal’s physiology. A genetics approach will also be used to identify neurotransmitters and endocrine signals potentially involved in the neural-immune communication that takes place between neurons and different tissues and infected sites. RELEVANCE (See instructions): The systemic control of innate immunity is critical because inflammation accounts for the major physiological, metabolic, and pathological responses to infections. We plan to continue our studies to clarify the role of the nervous system in the regulation of intestinal innate immune responses against bacterial pathogens. A better understanding of the neural-immune communication could lead to new therapeutic targets for diseases involving a deficient innate immune system.

越来越多的证据表明，肠道不仅在感知存在方面发挥着重要作用 病原体的变化，以及微生物群的变化，最终导致调节的变化 然而，免疫途径和行为的复杂性。 哺乳动物的神经和免疫系统使得剖析其机制变得困难 神经肠轴使用双向信号进行通信来控制肠道免疫研究。 线虫秀丽隐杆线虫表明细菌在肠道定植会导致 激活肠道先天免疫基因的表达和神经内分泌的激活 控制病原体回避的信号在神经肠轴中也起着关键作用。 不仅可以通过将免疫记忆传递给下一代，还可以通过交流 从肠道传播到神经系统以控制先天免疫的致病线索。 该提案的目标是阐明神经-种系-肠道轴的沟通机制 感知病原体和/或感染引起的生理变化，以控制先天免疫 因此，我们将探讨神经-种系-肠道轴发挥作用的一般假设。 通过帮助神经系统在针对细菌病原体的生物反应中发挥关键作用 整合来自感染部位和不同组织的信号来协调特定的免疫反应。 将研究基因和神经元，以剖析调节免疫激活的神经回路 对病原体暴露和病原体引起的动物生理变化的反应 A. 遗传学方法还将用于潜在地识别神经递质和内分泌信号 参与神经元和不同组织之间发生的神经免疫通讯 和受感染的地点。 相关性（参见说明）： 先天免疫的系统控制至关重要，因为炎症是主要的原因。 我们计划继续研究以阐明对感染的生理、代谢和病理反应。 神经系统在调节肠道针对细菌的先天免疫反应中的作用 更好地了解神经免疫通讯可能会带来新的治疗方法。 涉及先天免疫系统缺陷的疾病的目标。