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Neuroimmune interactions for laryngeal sensorimotor neuropathy in postviral influenza infection

病毒性流感感染后喉部感觉运动神经病变的神经免疫相互作用

基本信息

批准号：
10827254
负责人：
Alexander G Foote
金额：
$ 6.91万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-21 至 2026-08-20
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10827254
关键词：
ASCL1 gene Acute Address Affect Animals Attention Cell physiology Cells Chronic Clinical Treatment Coughing Data Diagnostic Disease Dysplasia Efferent Neurons Environment Epithelium Etiology Faculty Functional disorder Genetic Goals Health Hypersensitivity Image Immune Immune response Infection Inflammation Inflammatory Influenza A virus Injury Knockout Mice Laryngeal Epithelium Laryngeal Mucosa Laryngismus Larynx Link Lung Maps Mediating Mentors Modeling Motor Mucositis Mucous Membrane Nerve Neuroendocrine Cell Neuroimmune Neuroimmunomodulation Neurons Neuropathy Neurosecretory Systems Organ Outcome Paralysed Pathway interactions Peptides Physiology Population Postdoctoral Fellow Research Research Personnel Resolution Respiratory Signs and Symptoms Role Science Secretory Cell Sensorimotor functions Sensory Signal Transduction Specialist Testing Therapeutic Tissues Transgenic Animals Upper Respiratory Infections Upper respiratory tract Vagus nerve structure Viral Virus Virus Diseases Voice Work afferent nerve airway hyperresponsiveness arm cell type conditional knockout effective therapy efficacy testing experimental study improved influenza infection innovation insight mouse genetics mouse model mutant neural neural circuit neuroinflammation neuroregulation neurosensory neurotransmitter release novel programs repaired sensor sensory neuropathy therapeutic target transcriptome transcriptomics vocal cord

项目摘要

ABSTRACT The larynx is richly innervated with nerves, forming neuroimmune niches that constitute the basis for bidirectional interactions in mucosal defense and physiology. Idiopathic sensorimotor abnormalities of the larynx, such as acute vocal fold paralysis and chronic hypersensitivity (chronic cough, episodic laryngospasm) are attributed to upper respiratory tract infections with a viral etiology. However, a causal link for viral-induced laryngeal pathophysiology remains tenuous. In this application, I will employ an established model of influenza A virus (IAV) infection to interrogate laryngeal mucosal remodeling and map afferent/efferent neural circuits/cells in naïve and virus infected tissues. I will investigate the central hypothesis that viral infection of the larynx will activate neurosensory cells, remodel both afferent and efferent nerves, contributing to mucosal inflammation and hypersensitivity. I will test this hypothesis utilizing a combination of mouse genetics, whole tissue clearing and imaging, single-cell transcriptomics and live animal functional testing. We anticipate that these activated neural inflammatory signals are detected via a unique population of ASCL1+ neuroendocrine and CHAT+ cells that drive a neurosensory-immune circuit for laryngeal neuropathy. Together, these experiments are expected to ascertain neural sensorimotor circuits and reveal neuroimmune interactions for coordinating repair pathways following viral-induced mucosal inflammation. We expect findings will guide the field in new directions for innovating treatments for laryngeal and vocal fold inflammatory diseases and sensorimotor neuropathies.

摘要