Control of Mucociliary Clearance in Airway Host Defense

Respiratory infections remain a major threat to global health. To counter these insults, the respiratory system has evolved multilayered defense strategies that integrate anatomical and mechanical barriers with both innate and adaptive immune responses. Mucociliary clearance (MCC) serves as a cornerstone of airway host defense, whereby coordinated ciliary beating at the luminal surface of the airway epithelium drives the efficient removal of inhaled particles and pathogens. This process provides robust, broad-spectrum protection against both routine environmental exposures and emerging respiratory pathogens. In this Review, we summarize the current understanding of respiratory barrier function and defense strategies, with a particular emphasis on the immunological and metabolic mechanisms that regulate MCC. We further highlight the role of aldehyde dehydrogenases (ALDHs) in preventing ciliary damage and preserving MCC function, thereby conferring protection against environmental stress and respiratory infections.