Coordination of mucosal immune response to enteric bacterial pathogens by nociceptive innervation

通过伤害性神经支配协调对肠道细菌病原体的粘膜免疫反应

基本信息

批准号：
10591535
负责人：
Colin Reardon
金额：
$ 45.44万
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：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591535
关键词：
Ablation Address Affect Afferent Neurons American Bacterial Infections Blood Bone Marrow CCL19 gene CD4 Positive T Lymphocytes Cations Cell Adhesion Molecules Cells Chemotaxis Chimera organism Citrobacter rodentium Colon Communication Data Dendritic Cells Development Diphtheria Toxin Dissection Endothelial Cells Endothelium Enteral Enterocytes Epithelial Cells Escherichia coli EHEC Escherichia coli Infections Foundations Gastrointestinal tract structure Goals Hospitalization Host Defense Human Immune Immune response Immunity Immunologics In Vitro Infection Infectious Skin Diseases Inflammation Injury Innate Immune Response Intestinal Mucosa Intestines Knowledge Lamina Propria Lung Lung infections Lymphatic Endothelial Cells Lymphoid Cell Mechanics Mediating Modeling Monitor Morbidity - disease rate Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Neurogenic Inflammation Neuroimmune Neurokinin A Neurons Neurotransmitters Nociception Nociceptors Outcome Pathogenicity Island Peptides Permeability Physiological Process Production Role Sensory Skin Source Stimulus Substance P T-Lymphocyte TRPV1 gene Tissues Type III Secretion System Pathway Vasodilation adaptive immune response cell motility cell type chemokine enteric infection enteric pathogen enteropathogenic Escherichia coli experimental study health determinants host-microbe interactions immune function in vivo innovation interleukin-22 intestinal epithelium member migration mortality nerve supply neurotransmitter release novel pathogen pathogenic bacteria prevent protein expression receptor recruit response therapeutic target

项目摘要

Project Summary Host-microbial interactions are a critical determinant of health. The gastrointestinal tract provides several overlapping mechanisms that function together to prevent entry of pathogens into the body. These protective mechanisms are provided through the coordinated of intestinal epithelial cells and immune cells in the lamina propria. While the specialized sensory nociceptive neurons that detect noxious stimuli such as pathogens, or the resulting host tissue damage are known to control immune function in the skin and lung, the contribution of these neurons to intestinal mucosal immunity is not known. Building on our preliminary data, the overall goals of this project are to precisely determine the role of sensory nociceptive neurons in the neuro-immune communication that limits enteric bacterial infection. This will be achieved by selective ablation of sensory neurons, and experiments to determine the source of SP and the targeted cells (SA1). How an enteric bacterial pathogen induces nociceptive activation in vitro and in vivo (SA2). Mechanistic understanding of the immunological effect of sensory neurons during enteric infection will be attained. Specifically, how nociceptor ablation impinges on dendritic cell migration, chemokine production, and adhesion molecule expression will be determined (SA3). Together, these proposed studies will decipher the contribution of sensory afferent nociceptive neurons to mucosal host defense during enteric bacterial infection.

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。胃肠道提供几种重叠的机制共同发挥作用，防止病原体进入体内。这些保护机制是通过肠上皮细胞和固有层中的免疫细胞。虽然专门的感觉伤害性神经元检测已知病原体等有害刺激或由此产生的宿主组织损伤可以控制免疫尽管这些神经元在皮肤和肺中发挥功能，但它们对肠粘膜免疫的贡献并不大已知。根据我们的初步数据，该项目的总体目标是准确确定限制肠道细菌感染的神经免疫通讯中的感觉伤害神经元。这将通过选择性消融感觉神经元并进行实验来确定来源来实现 SP 和靶细胞 (SA1)。肠道细菌病原体如何诱导伤害性激活体外和体内（SA2）。感觉神经元免疫效应的机制理解在肠道感染期间就会达到。具体来说，伤害感受器消融如何影响树突状细胞将确定迁移、趋化因子产生和粘附分子表达（SA3）。总之，这些拟议的研究将破译感觉传入伤害性神经元的贡献肠道细菌感染期间粘膜宿主防御。