Date on Master's Thesis/Doctoral Dissertation
5-2024
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Microbiology and Immunology
Degree Program
Microbiology and Immunology, PhD
Committee Chair
Bagaikar, Juhi
Committee Co-Chair (if applicable)
Sokoloski, Kevin
Committee Member
Lamont, Richard J.
Committee Member
Chung, Donghoon
Committee Member
Casella, Carolyn
Author's Keywords
gingivalis; interferon; anti-viral; oral; respiratory; mucosa
Abstract
The host microbiome plays an important role in fine-tuning host immune responses in a manner that ultimately impacts outcomes in viral infection. Symbiotic relationships between commensal bacteria and host epithelial and immune cells prime interferon (IFN) signaling, modulating the nature and intensity of the immune response to viral infections at mucosal barrier surfaces. In this doctoral thesis, I explore how dysbiotic shifts in the oral microbial communities modulate antiviral responses at the oral and oro-respiratory mucosal barriers. I identified that in response to a viral challenge, gingival epithelial cells (GECs) preferentially induced type III IFNs (IFN-λ), a newly described family member of the interferon family that plays a superior role in regulating antiviral immunity at barrier surfaces. While IFN-λ strongly activated multiple interferon-stimulated genes (ISGs) in human gingival epithelial cells. However, IFN-λ responses were significantly dampened in the presence of Porphyromonas gingivalis, an oral periodontal pathogen. Mechanistically, P. gingivalis virulence factors inactivated IFN-inducing transcription factors and suppressed IFN promoter activity, subsequently dampening ISG induction. This was coupled with the proteolytic degradation of IFN receptors by P. gingivalis proteases, gingipains, inducing refractoriness to exogenous IFN stimulation. Overall, P. gingivalis induced suppression of IFN signaling significantly enhanced host susceptibility to viral infection of oral epithelial cells. Furthermore, I found that P. gingivalis mediated IFN suppression was not limited to the oral epithelium but also impacted airway epithelial cells in a similar manner. In conclusion, my data highlights how a bacterial pathogen associated with oral dysbiosis can significantly impact susceptibility to viral infections at both oral and respiratory barriers.
Recommended Citation
Rodriguez Hernandez, Carlos J., "Porphyromonas gingivalis inactivates anti-viral immunity at the oral and respiratory epithelium." (2024). Electronic Theses and Dissertations. Paper 4305.
https://doi.org/10.18297/etd/4305
