JAX CCHI-Modulation of Lung Responses to Viral Infection- ALI SARS-CoV-2

Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia. Use of lung donors from NDRI to make organoids, then lung organoid-derived air-liquid interface (ALI) cultures with infection of SARS-CoV2 like virus or mock. To better understand the early spatiotemporal events happening in lung epithelium during SARS-CoV-2 infection and their potential biological consequences, we based our study on an in vitro model of primary human airway epithelial cells: air-liquid interface (ALI) cultures generated from human lung organoids from healthy donors. Such cultures effectively recapitulate in vivo airway epithelium architecture and we validated their permissibility to viral infection by exposure to SARS-CoV-2 (Wuhan-like, USA/WA1-2020) and its variants (Beta, Delta and Omicron BA.1 subvariant). Our findings reveal spatiotemporal regulation of cytokines, chemokines and suggest that different cells in the lung epithelium may regulate different aspects of immune response to SARS-CoV-2. Furthermore, the use of lung organoid-derived ALI from a variety of donors revealed differential infection dynamics reflecting biological differences between individuals, potentially explaining some of the diverse clinical outcomes observed between patients.