Respiratory Epithelial Cells Can Remember Infection: A Proof-of-Concept Study

Abstract

Human bronchial epithelial cells play a key role in airway immune homeostasis. We hypothesized that these sentinel cells can remember a previous contact with pathogen compounds and respond nonspecifically to reinfection, a phenomenon called innate immune memory. We demonstrated that their preexposure to Pseudomonas aeruginosa flagellin modify their inflammatory response to a second, nonrelated stimulus, including live pathogens or lipopolysaccharide. Using histone acetyltransferase and methyltransferase inhibitors, we showed that this phenomenon relied on epigenetic regulation. This report is a major breakthrough in the field of multimicrobial respiratory tract infections, wherein control of inflammatory exacerbations is a major therapeutic issue.

Keywords: bronchial epithelial cells; infection; inflammation; innate immune memory; trained immunity.