Thesis Format
Integrated Article
Degree
Master of Science
Program
Microbiology and Immunology
Supervisor
Prodger, Jessica L.
2nd Supervisor
Troyer, Ryan M.
Co-Supervisor
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.
Summary for Lay Audience
The lining of our nasal passages or the nasal mucosa acts as a barrier between the environment and our airways. When respiratory viruses breach this defense, they can cause severe illnesses especially if they reach the lungs as seen in the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronaviurs-2 (SARS-CoV-2). Due to the importance of this virus, the nasal immune responses after SARS-CoV-2 infection have been extensively investigated. However, we don’t fully understand how the innate immune state, the body’s natural defense system, affects our susceptibility to this virus.
To investigate the innate immune aspect, we created a model of the nasal mucosa in the lab. Cells were taken from human nasal tissues and grown, using a technique called air-liquid interface, into a layer that mimics the structure and function of the natural respiratory lining. We characterized the layer through imaging to ensure structural representation. Once developed, we treated the matured models with two different combinations of cytokine that we previously found to naturally exist within the nasal cavity of adults and infected the layers with SARS-CoV-2.
In this study, I showed through imaging that our nasal model mimics our mucosal lining. Our preliminary data suggests that the cytokines promoting inflammation slightly increase susceptibility to SARS-CoV-2, whereas cytokines that enhanced anti-viral defenses protected against infection.
This work established methods for growing imaging a nasal mucosa and highlighted the potential of the existing innate immune environment to affect SARS-CoV-2 susceptibility. These important developments lay the foundation for future research into how the nasal microbiome and other respiratory viruses might interact with our nasal immune system to protect or harm us.
Recommended Citation
Lam, Victor H.K., "Characterizing and Applying a Nasal Organotypic Model to Investigate the Effects of Immune Profile Types on SARS-CoV-2 Susceptibility" (2024). Electronic Thesis and Dissertation Repository. 10108.
https://ir.lib.uwo.ca/etd/10108
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cells Commons, Immunology of Infectious Disease Commons, Respiratory System Commons, Tissues Commons, Virology Commons