The nose-lung cross talk in upper respiratory virus infection induced asthma exacerbations

上呼吸道病毒感染引起的哮喘加重中的鼻肺交互作用

• 批准号: 10733754
• 负责人: Xiaoyang Hua
• 金额: $ 62.22万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733754
• 关键词: Adjuvant; Adoptive Cell Transfers; Affect; Allergens; Antigen-Presenting Cells; Antigens; Asthma; B-Lymphocyte Subsets; B-Lymphocytes; Bone Marrow; Bronchoalveolar Lavage Fluid; CCL2 gene; CCL7 gene; Cells; Coronavirus; Data; Development; Disease; Dose; Exposure to; Goals; Homing; Human; IL5 gene; Immune; Immune response; Immunity; Immunocompromised Host; Immunologics; Immunology; Immunomodulators; Infection; Inflammation; Inflammatory; Inflammatory Response; Ingestion; Lung; Lung infections; Measures; Molecular; Mucosal Immune System; Mucous Membrane; Mucous body substance; Mus; Natural Immunity; Nose; Outcome; Patients; Physiology; Play; Preventive; Production; Pyroglyphidae; Reporting; Research; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Structure of mucous membrane of nose; Therapeutic; Viral Load result; Viral Respiratory Tract Infection; Virus; Virus Diseases; Virus Shedding; adaptive immunity; airway hyperresponsiveness; airway inflammation; asthma exacerbation; asthmatic; chemokine; cytokine; draining lymph node; humoral immunity deficiency; lymph nodes; migration; monocyte; novel; pathogen; recruit; respiratory infection virus; response; trafficking; vaccine development; vaccine immunotherapy

Project Summary Upper respiratory virus infection (URVI) is the leading cause of asthma exacerbation episodes. The underlying immunologic mechanisms are poorly understood. Particularly, it remains unknown if URVI-induced asthma exacerbation is exclusively a result of direct viral infection in the lower airway and lungs, in the nose and upper airway, or both. Previous study has shown that the viruses commonly associated with asthma attacks were not detected in the lungs of patients who died of asthma attacks. Recently, we observed that nasal virus infection can remotely activate lung immunity without direct lung antigenic exposure. Nasal viral infection can recruit antigen presenting cells (APCs) in the lungs. These activated APCs ingest antigen and migrate to pulmonary lymph nodes, enhancing both innate and adaptive immunity to unrelated antigens in the lungs. Our data have suggested that nasal mucosa can remotely regulate lung immunity without direct lung antigenic exposure (aka “nose-lung cross talk”). Such nose-lung cross talk may also play a key role in URVI induced asthma exacerbations. In the proposed study, we will 1) define the immune mechanisms underlying the nose-lung cross talk after nasal viral infection; 2) determine the airway physiology airway inflammation after nasal viral infection in mice with experimental asthma and the mechanisms by which URVI indued asthma exacerbations. Completion of this project is expected to advance our understanding of the mechanisms underlying URVI induced asthma exacerbations, and to identify new preventative and therapeutic strategies for asthmatics. It will also further define airway mucosal immunology, particularly the immune network underlying the nose-lung cross talk, and to facilitate novel directions in nasal vaccine development and immunotherapy for diseases that affect both the nose and lungs.

项目摘要 上呼吸道病毒感染（URVI）是哮喘恶化发作的主要原因。基础 免疫机制知之甚少。特别是，是否尚不清楚URVI诱发哮喘 恶化仅是下部气道和肺部，鼻子和上部直接病毒感染的结果 气道或两者兼而有之。先前的研究表明，通常与哮喘发作相关的病毒不是 在死于哮喘发作的患者的肺中发现。最近，我们观察到鼻病毒感染 可以远程激活肺免疫，而无需直接肺抗原暴露。鼻病毒感染可以招募 肺中的抗原呈递细胞（APC）。这些激活的APC摄入抗原并迁移到肺部 淋巴结，增强对肺无关抗原的先天和适应性免疫学。我们的数据有 建议鼻粘膜可以远程调节肺免疫，而无需直接肺抗原暴露（又称 “鼻肺交谈”）。这种鼻肺串扰也可能在URVI引起的哮喘中起关键作用 恶化。在拟议的研究中，我们将1）定义鼻 - 肺肺部的免疫力学 鼻病毒感染后的串扰； 2）确定鼻病毒后气道生理气道注射 实验性哮喘的小鼠感染以及URVI导致哮喘恶化的机制。 预计该项目的完成将提高我们对URVI潜在机制的理解 引起哮喘加重，并确定哮喘患者的新预防和治疗策略。 还将进一步定义气道粘膜免疫学，尤其是鼻肺的免疫网络 交谈，并促进鼻疫苗发育和免疫疗法的新方向 影响鼻子和肺部。