Abstract
Mucus plays a pivotal role in protecting the respiratory tract against microbial infections. It acts as a primary contact site to entrap microbes and facilitates their removal from the respiratory tract via the coordinated beating of motile cilia. The major components of airway mucus are heavily O-glycosylated mucin glycoproteins, divided into gel-forming mucins and transmembrane mucins. The gel-forming mucins MUC5AC and MUC5B are the primary structural components of airway mucus, and they enable efficient clearance of pathogens by mucociliary clearance. MUC5B is constitutively expressed in the healthy airway, whereas MUC5AC is upregulated in response to inflammatory challenge. MUC1, MUC4, and MUC16 are the three major transmembrane mucins of the respiratory tracts which prevent microbial invasion, can act as releasable decoy receptors, and activate intracellular signal transduction pathways. Pathogens have evolved virulence factors such as adhesins that facilitate interaction with specific mucins and mucin glycans, for example, terminal sialic acids. Mucin expression and glycosylation are dependent on the inflammatory state of the respiratory tract and are directly regulated by proinflammatory cytokines and microbial ligands. Gender and age also impact mucin glycosylation and expression through the female sex hormone estradiol and age-related downregulation of mucin production. Here, we discuss what is currently known about the role of respiratory mucins and their glycans during bacterial and viral infections of the airways and their relevance for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the impact of microbe-mucin interaction in the respiratory tract could inspire the development of novel therapies to boost mucosal defense and combat respiratory infections.
Highlights
Mucus plays a pivotal role in protecting the respiratory tract against microbial infections
We summarize what is known about the respiratory mucosal defense system in the context of bacterial and viral infections and discuss its importance during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
The major mucins produced in the airways are soluble mucins MUC5AC and MUC5B, which are secreted by goblet cells, and the transmembrane mucins MUC1, MUC4, and MUC16, which are expressed on the apical surface of all epithelial cell types along the different tissues of the respiratory tract [5]
Summary
Expression of soluble and transmembrane mucins is increased, and their glycosylation is altered to boost mucosal defense Several studies have reported that the terminal sugars of mucin O-glycans and, sialic acids play a key role in interactions with respiratory pathogens. A recent study reported that the extracellular domain of MUC1 can act as a releasable decoy molecule during P. aeruginosa infection, thereby restricting pathogen adherence to the epithelial surface [35]. Ligand binding and recognition could be hampered by the formation of a MUC1-TLR receptor complex, preventing direct interaction of pathogens with the epithelial cell surface. The existing data indicate that MUC1 plays an important anti-inflammatory role during infection with different bacterial pathogens at the respiratory mucosa. Transmembrane mucins during airway infection needs to be addressed thoroughly to understand mucin-specific functions
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