CC16 mediated epithelial-driven host responses to Rhinovirus infection is defective in nasal cells from asthma patients 3802

Abstract Description Rhinovirus (RV) increases the risk for developing asthma and is the major trigger for disease exacerbations. CC16 is produced and secreted by club cells and non-ciliated epithelial cells in the pulmonary epithelium and reduces inflammatory responses in the lungs and has phospholipase A2 inhibiting activity. Moreover, CC16 levels are decreased in asthma patients, which are associated with more frequent exacerbations. This study aims to determine the impact of CC16 on RV-1B infection using human nasal epithelial cells (HNECs) from asthma and non-asthma participants cultured in air-liquid interface system in the presence or absence of recombinant CC16 (rCC16). Viral RNA and the expression of host defense factors including Lysozyme, SPLUNC1, Lactotransferrin, Surfactant protein A, Surfactant protein-D were quantified by RT-qPCR. We found higher RV burden and lower CC16 in HNECs isolated from asthmatic individuals. RV infection increased host defense factors in non-asthmatic but not asthmatic HNECs. rCC16 induced the expression of host defense factors and reduced viral burden in HNECs from both groups. In addition, the CC16-mediated host defenses that were diminished in asthmatic HNECs were rescued by exogenous delivery of rCC16 during infection. These results suggest that CC16 can reduce rhinovirus infection in nasal epithelial cells by mediating the upregulation of host defense factors and that this mechanism may be defective in asthma patients due to low levels of CC16. Funding Sources NIH HL142769 and the Flinn Foundation Topic Categories Viral Immunology (VIR)