Airway mucus in infection

The mucosa of the airways is under a near-constant barrage of contaminants, allergens, and pathogens that can accumulate and cause irritation or infection if not promptly removed. Mucus, composed of a mucin glycoprotein mesh, protects the airways from these contaminants by entrapment and removal. Several diseases stall the protection provided by the mucus by altering its components and biophysical properties. This review provides an overview of how the defensive mucus of the airways functions in health, how the mucus can fail to clear with muco-obstructive lung diseases, how mucins respond to pathogens that infect the mucus, how the molecular signals of mucin secretion function, and how therapeutics may improve morbidity and mortality for people with muco-obstructive lung disease. Recent studies of the spatial organization of mucin-producing cells have led to new understanding of the difference between constitutive MUC5B production by superficial epithelial cells and between trigger-induced production and secretion by the goblet cells and submucosal glands. The coordination of mucin production and secretion with ion and water homeostasis is discussed to evaluate how changes in sodium, calcium, bicarbonate, and chloride are responsible for failures of mucin unfolding and the subsequent biophysical properties of the mucus. Rheological and inflammatory characteristics of the muco-obstructive lung diseases are compared to determine how the defect in mucus clearance leads to distinct morbidity and mortality with attention paid to the microbial pathogens prevalent between groups. The distinctions between the molecular mechanisms of mucin production and secretion within muco-obstructive lung diseases are discussed with a focus on several cytokines such as IL-1β, secretagogues like ATP, and protein chaperones such as ERN2. Pathogenic induction of mucin production and secretion are discussed with primary focus on bacterial mediators. Finally, established and novel therapies for muco-obstructive lung diseases are discussed for potential at improving mucociliary clearance defects and for reducing exacerbation.