Mucus, Microbiomes and Pulmonary Disease - PubMed (original) (raw)

Review

Mucus, Microbiomes and Pulmonary Disease

Oliver W Meldrum et al. Biomedicines. 2021.

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.

Keywords: microbiome; mucin; mucus; pulmonary disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

The polymeric and macromolecular structure of polymerizing airway mucins. (A) The mucin backbone is the primary site of O-linked glycosylation (Core 1–4) that attach to (B) serine-, threonine-, and proline-rich amino acids (green). These regions are interspersed with cysteine-rich regions (CysD domains, red) containing hydrophobic amino acids and intramolecular disulfide bonds. (C) The mucin monomer contains C- and N-termini as sites of intermolecular disulfide bonds that (D) assemble into multimer states that exist as linear, branched, or side-linked structures. The mucus gel is a dynamic network, subject to removal and reformation of chemical and physical interactions via disulfide bonds and entanglement from low-energy electrostatic and hydrophobic interactions, respectively.

Figure 2

Figure 2

Airway localization of polymerizing mucins. Regional distribution of MUC5AC (red) and MUC5B (green) mucin glycoproteins along the proximal–distal axis of normal airway epithelia with neither MUC5AC nor MUC5B expressed in the terminal bronchioles or alveoli. MUC5B (MUC5B+) is the dominant secretory mucin in submucosal glands and superficial airway epithelia, while MUC5AC (MUC5AC+) is secreted into the superficial epithelial lining in the proximal airways and locates alongside non-polymerizing mucin club cell secretory protein (CCSP+)-expressing cells. These polymerizing mucins overlay the periciliary layer (PCL) and are propagated by mucociliary action out of the lungs. Adapted from data presented in [26].

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