Genetic analysis of innate immunity using C. elegans

越来越多的证据表明，肠道不仅在感知存在的过程中发挥着重要作用 以及微生物区系的变化，这最终导致调节的变化 通过与神经元交流的免疫途径和行为。然而，这个问题的复杂性 哺乳动物的神经和免疫系统使我们很难剖析 神经-肠轴使用双向信号进行通信，以控制肠道免疫。在美国的研究 线虫秀丽线虫表明，肠道的细菌定植导致 肠道天然免疫基因表达的激活和神经内分泌的激活 控制病原体避免的信号。生殖系在神经肠轴中也起着关键作用。 不仅通过将免疫记忆传递给下一代，还通过沟通 从肠道传播到神经系统以控制先天免疫的致病线索。长期的 这项建议的目的是阐明神经-生殖线-肠轴的沟通机制。 感知病原体和/或感染引起的生理变化，以控制先天免疫 整个动物的水平。因此，我们将探索神经-生殖线-肠轴起作用的一般假设。 通过帮助神经系统在机体对细菌病原体的反应中起关键作用 整合来自感染部位和不同组织的信号，以协调免疫反应。特定的 将对基因和神经元进行研究，以剖析调节免疫激活的神经回路 对病原体暴露和病原体诱导的动物生理变化的反应。一个 遗传学方法也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 和受感染的地方。 相关性(请参阅说明)： 对先天免疫的系统控制是至关重要的，因为炎症是主要的 对感染的生理、代谢和病理反应。我们计划继续我们的研究以澄清 神经系统在肠道抗细菌天然免疫反应调节中的作用 病原体。更好地了解神经免疫通讯可能会带来新的治疗方法 针对涉及先天免疫系统缺陷的疾病。

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.