Airway mucus, infection, and therapeutic strategies

The respiratory tract epithelium is hydrated by a mucous layer, which forms a protective barrier for the defense against sometimes life-threatening foreign particles, including bacteria and viruses. The mucous layer is fluid in nature and facilitates ciliary beating, enabling mucociliary clearance. The mucus consists of a complex array of macromolecules called mucins, which are linked to complex long carbohydrate chains called O-glycans. Certain debilitating disorders such as cystic fibrosis, and even the recent COVID-19 can lead to the impairment of this layer by affecting its transport properties. In turn or individually, pathogens of the respiratory tract can evade this barrier by directly interacting with the intact mucus and bypassing it or by surviving in the already damaged layer. Therefore, understanding the specificities of mucin dysfunction and the mucin-pathogen relationship in immunocompromised infections is important for the development of therapeutics targeting mucin-associated mechanisms.