Abstract
The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.
Highlights
The Structure and Function of Pulmonary MucusThe surface of intrapulmonary airways is dominated by ciliated and secretory cell types [23]
Introduction and Pulmonary DiseaseBiomedicinesPneumonia remains one of the leading causes of morbidity and mortality globally, with nearly 2.3 million deaths reported in 2016
While any individual may develop respiratory infection and/or pneumonia, risks are higher in those with chronic airways disease such as asthma [5], cystic fibrosis (CF) [6], non-CF bronchiectasis [7], and chronic obstructive pulmonary disease (COPD) [8,9], whose disease course is punctuated by episodes of recurrent infection and exacerbation which, in turn, increases mortality risk
Summary
The surface of intrapulmonary airways is dominated by ciliated and secretory cell types [23]. Airway mucus represents a multi-component secretion best described as a biological hydrogel composed of water, polymerizing mucin glycoproteins (MUC5B and MUC5AC), a range of antimicrobial molecules (defensins, lysozyme, etc.), cellular components (cellular debris including DNA and keratin), and protective factors (trefoil factors) [25]. All such components are perpetually synthesized, secreted, and integrated into mucus before appropriate degradation and clearance. Neither is expressed in the terminal bronchioles, suggesting that gas exchange requires a surfactant-rich, mucin-free zone to protect adjacent alveoli
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