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

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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.