Date of Award

January 2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

First Advisor

Nadeem Khan

Abstract

Influenza virus continues to cause severe disease globally, especially in elderly and immunocompromised populations. While at-risk populations are encouraged to get the yearly influenza vaccine, high mutation rates of the virus result in seasons of diminished vaccine efficacy. While there is an apparent need to devise an influenza vaccine to fight antigenic drift, research has also currently been pushing toward investigating the pathological response to influenza disease. More specifically, how the dysregulation in the host immune response contributes to influenza disease pathology in the lungs. The importance of dissecting the mechanism at which influenza-mediated tissue pathology occurs is an important and necessary step in formulating targeted therapeutics to modulate the host immune system and minimize risk to influenza-related complications. Herein, two roles for IFN-gamma in the development of influenza-mediated tissue pathology is described. First, the regulation of the inflammatory/pathological phenotype of CCR2 monocytes duringinfluenza infection, and second; promoting dysregulation and barrier injury of lung epithelia via suppression of epithelial IL6R-STAT3 reparative mechanisms. These findings contribute to the field the foundation for future mechanistic studies to dissect host pathological response to influenza disease.

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