Doris Wilflingseder: Infections in a dish: Innate Defense to Respiratory Viruses in Species-Specific Airway Models

Infections in a dish: Innate Defense to Respiratory Viruses in Species-Specific Airway Models

The airway epithelium functions as a dynamic immune barrier where epithelial and myeloid programs coordinate early defense against respiratory pathogens. Using advanced air-liquid interface and immune-competent 3D models, recent work delineates barrier-intrinsic mechanisms spanning epithelial complement activation, mucus remodeling and hypersecretion, and integrity loss under viral challenge. Variant-dependent responses in epithelial and immune cells reveal distinct inflammatory-metabolic states. Translational studies demonstrate the respiratory safety and uptake of inhaled siRNA and identify barrier-targeted prophylactics with broad antiviral potential: low–molecular-weight heparin reduces influenza infection and epithelial damage, while a glycerol-based mouth spray lowers rhinovirus burden, symptom duration, and barrier disruption in vitro and in athletes. Complement-engaging epithelial responses to aero-exposures are captured and together, these findings support a microenvironment-centric framework that integrates complement, tissue resident immune cells, mucus, and metabolic regulation to limit infection and tissue injury.

Wilflingseder Laboratory