Neuro-immune mediated control of mucosal immunity

神经免疫介导的粘膜免疫控制

基本信息

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
项目类别：
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

项目摘要

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：宿主与微生物的相互作用是健康的关键决定因素。肠粘膜提供多种不同的重叠机制共同发挥作用，降低病原体的能力获得进入身体的机会。这些保护机制主要是由专门的肠道提供的上皮细胞可以产生粘液和杀菌抗菌肽。虽然已经很久了已知神经递质控制这一过程，人们曾假设这些起源于神经元。最近，我们发现了一个独特的 B 细胞和 T 细胞子集，可以产生神经递质乙酰胆碱，在肠道细菌感染期间专门招募。该项目的总体目标是确定这些独特的 B 细胞和 T 细胞的作用并阐明引起的保护机制。这将通过使用中和抗体来实现条件敲除小鼠破译这些细胞在感染过程中的作用（SA1）。确定是否有这些 B 细胞和 T 细胞通过增加粘液产生和释放来保护宿主，将在 SA2。这些细胞诱导抗菌肽表达的能力也将在 SA2 中进行评估。总之，这些拟议的研究将破译独特的免疫细胞群对粘膜宿主防御。