In vitro modeling of influenza infection in the respiratory epithelium: advanced cellular models to better understand complex host–virus interactions

Influenza viruses pose significant global health threats, causing widespread morbidity and mortality due to their genetic variability and rapid evolution. Traditional experimental models, such as immortalized cell lines and animal models, often fall short of accurately replicating the complex interactions between influenza viruses and the human immune system. Recent advancements, including reconstituted human airway epithelia, lung-on-a-chip models, and human airway organoids, provide more accurate representations of human respiratory physiology and immune responses. These alternatives enable in-depth investigations into viral propagation, host immune responses, and tissue damage. While each model has its unique advantages and limitations, integrating them could offer a more comprehensive understanding of influenza pathogenesis. This knowledge can drive the development and evaluation of more effective vaccines and therapeutic interventions, enhancing preparedness for future influenza outbreaks.