Neuro-immune mediated control of mucosal immunity

神经免疫介导的粘膜免疫控制

• 批准号: 9373065
• 负责人: Colin Reardon
• 金额: $ 22.8万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-09 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9373065
• 关键词: Acetylcholine; Address; Autonomic nervous system; B-Lymphocyte Subsets; Bacterial Infections; CD4 Positive T Lymphocytes; CXCL13 gene; Cell physiology; Cells; Choline O-Acetyltransferase; Citrobacter rodentium; Colon; Enteral; Enterocytes; Enzymes; Epithelial Cells; Escherichia coli EHEC; Foundations; Goals; Goblet Cells; Growth; Health; Host Defense; Human; Immune; Immune response; Immunity; Infection; Inflammatory disease of the intestine; Intestinal Mucosa; Intestines; Knockout Mice; Knowledge; Lymphocyte; Macrophage Activation; Mediating; Modeling; Mucosal Immune Responses; Mucosal Immunity; Mucous body substance; Mus; Neuroimmune; Neurons; Neurotransmitters; Outcome; Pathogenesis; Pathogenicity Island; Peripheral; Population; Process; Production; Recruitment Activity; Reflex action; Regulation; Role; Severities; Signal Transduction; Symbiosis; T-Lymphocyte; TNF gene; Testing; Tissues; Type III Secretion System Pathway; Vagotomy; adaptive immune response; antimicrobial peptide; bactericide; chemokine; cholinergic neuron; enteropathogenic Escherichia coli; expectation; host-microbe interactions; in vivo; innovation; insight; interest; microbiota; neuroinflammation; neurotransmission; neutralizing antibody; pathogen; prevent; response

Project summary: Host-microbial interactions are a critical determinant of health. The intestinal mucosa provides serval distinct overlapping mechanisms that function together in concert to reduce the ability of pathogens to gain access to the body. These protective mechanisms are largely provided by specialized intestinal epithelial cells that can produce mucous and bactericidal antimicrobial peptides. While it has long been known that neurotransmitters control this process, it had been assumed that these originated from neurons. Recently we have identified a unique subset of B- and T-cells that produce the neurotransmitter acetylcholine, and that are specifically recruited during enteric bacterial infection. The overall goals of this project are to determine the role of these unique B- and T-cells and elucidate the mechanisms of protection that are elicited. This will be achieved by using neutralizing antibodies and conditional knockout mice to decipher the role of these cells during infection (SA1). Determining if these B- and T-cells are protective to the host by increasing mucous production and release will be assessed in SA2. The ability of these cells to induce expression of antimicrobial peptides will also be assessed in SA2. Together, these proposed studies will decipher the contribution of a unique immune cell population to mucosal host defense.

项目概要： 宿主-微生物相互作用是健康的一个关键决定因素。肠粘膜提供了大量的 不同的重叠机制，共同发挥作用，以减少病原体的能力， 能接触到尸体这些保护机制主要是由专门的肠道 能产生粘液和杀菌性抗菌肽的上皮细胞。虽然长期以来 已知神经递质控制这一过程，人们一直认为这些神经递质来源于 神经元最近，我们已经确定了一个独特的B-和T-细胞亚群，它们产生 神经递质乙酰胆碱，并且在肠道细菌感染期间特异性募集。 该项目的总体目标是确定这些独特的B和T细胞的作用，并阐明 所引发的保护机制。这将通过使用中和抗体来实现， 条件性基因敲除小鼠以解读这些细胞在感染期间的作用（SA 1）。确定这些 B细胞和T细胞通过增加粘液产生和释放对宿主具有保护作用，将在 SA 2.还将在SA 2中评估这些细胞诱导抗微生物肽表达的能力。 总之，这些拟议的研究将破译一个独特的免疫细胞群的贡献， 粘膜宿主防御