Antimicrobial polypeptides in host defense of the respiratory tract

The large surfaces of the respiratory tract are often the initial site of contact between microbes and their human hosts. Respiratory epithelia are coated with a thin layer of airway and alveolar secretions whose composition varies by anatomical location and in response to mechanical, chemical, and microbial stimulation. In the nose, trachea, and bronchi, the secretions are generated by airway epithelial cells, especially the goblet cells; by the submucosal glands; by transudation and transport of proteins from plasma; and by resident and recruited phagocytes — neutrophils, eosinophils, monocytes, and macrophages. In the distal airways and alveoli, Clara cells and type 2 alveolar cells are, respectively, the predominant secretory epithelial cells. As first described by Alexander Fleming nearly 80 years ago (1), respiratory secretions have microbicidal and microbistatic properties mediated by their constituent antimicrobial polypeptides. These intrinsic antimicrobial properties of respiratory secretions act in concert with the mechanical and phagocytic clearance mechanisms, described elsewhere in this Perspective series, to defend the respiratory tract against colonization or invasion by environmental microbes.