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

项目摘要 上呼吸道病毒感染（URVI）是哮喘急性发作的主要原因。底层 免疫机制知之甚少。特别是，目前尚不清楚URVI引起的哮喘是否 急性加重完全是下呼吸道和肺、鼻和上呼吸道中的直接病毒感染的结果。 气道或两者。先前的研究表明，通常与哮喘发作有关的病毒并不 在死于哮喘发作的病人的肺部检测到。最近，我们观察到鼻病毒感染 可以远程激活肺免疫而不直接暴露于肺抗原。鼻病毒感染可以招募 肺内的抗原呈递细胞（APC）。这些活化的APC摄取抗原并迁移到肺 淋巴结，增强对肺中不相关抗原的先天性和适应性免疫。我们的数据 提示鼻粘膜可以在不直接暴露肺抗原的情况下远程调节肺免疫（aka "鼻肺串扰"）。这种鼻肺串扰也可能在URVI诱导的哮喘中起关键作用 加重在拟议的研究中，我们将1）定义鼻肺的免疫机制 鼻病毒感染后的气道生理学变化; 2）鼻病毒感染后的气道炎症 感染实验性哮喘小鼠和机制，其中URVI诱导哮喘恶化。 该项目的完成有望促进我们对URVI机制的理解 诱发哮喘急性发作，并确定新的预防和治疗哮喘的策略。它 还将进一步定义气道粘膜免疫学，特别是鼻-肺下的免疫网络 串扰，并促进鼻疫苗开发和免疫治疗疾病的新方向， 影响鼻子和肺。

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.