Characterizing and Applying a Nasal Organotypic Model to Investigate the Effects of Immune Profile Types on SARS-CoV-2 Susceptibility
Abstract
The nasal mucosa is the first line of defense against respiratory pathogens. While early responses to viral infections are well-documented, the influence of the pre-existing nasal immune environment on susceptibility to respiratory pathogens remain unclear. This thesis investigates the impact of the pre-existing nasal immune milieu on susceptibility to SARS-CoV-2. An in vitro nasal model was developed, consisting of primary airway epithelial cells differentiated at the air-liquid interface to generate a mucociliary epithelium capable of supporting SARS-CoV-2 infection. Matured nasal epithelia were pre-treated with key cytokines before SARS-CoV-2 Omicron (BA.1) challenge. Preliminary findings indicate that a highly inflammatory milieu exacerbates viral production compared to unstimulated control. This work established culturing and imaging techniques for organotypic pseudostratified epithelia and is the first to explore the influence of the existing immune milieu on viral susceptibility. These results lay the groundwork for future studies investigating the effect of nasal exposures on respiratory pathogens.