Respiratory Epithelial Memory: Uncovering the role of trained immunity in the respiratory epithelium

Objective

Immunological memory, once thought to be exclusive to the adaptive immune system, is now increasingly recognized as a feature of innate immunity. This phenomenon, known as trained immunity, enables innate immune cells to undergo lasting functional changes after an initial infection, improving their response to future immune challenges. While trained immunity is well characterized in some cell types, its role in non-immune cells such as epithelium remains understudied. Respiratory epithelium is a major site of pathogen exposure, and recent studies hint at the ability for respiratory epithelial cells to undergo trained immunity. This project will provide a comprehensive analysis of trained immunity in the respiratory epithelium using a physiologically relevant in vitro model of human airway epithelium. An interdisciplinary approach will be used to characterize metabolic, epigenomic, transcriptomic, and proteomic changes associated with the trained phenotype. Functional relevance will be assessed through viral challenge experiments, and findings will be validated using clinical respiratory cell samples collected after viral infection. Altogether, this work will expand the understanding of trained immunity in barrier tissues and may reveal novel therapeutic targets for preventing and treating respiratory infections.