Figure 1.

Schematic representation of the tripartite symbiosis model between bacteriophages, bacteria and epithelium within healthy (A) and asthmatic (B) airways. (A) Healthy epithelium of large and small airways of the lungs is constituted by basal, ciliated and secretory Goblet (large airways) or Clara cells (small airways) that form pseudostratified or columnar and cuboidal structures, respectively. Epithelial barrier integrity is ensured by the formation of intracellular Tight Junctions (TJs) and by the secretion of mucus by Goblet or Clara cells. Healthy epithelium physically controls bacterial populations and eliminates bacterial invasion through mucociliary clearance (MCC). In healthy airways there is a diverse population of bacteria and bacteriophage communities that interact directly through lysis-lysogeny mechanisms and horizontal gene transfer as represented in the figure. Bacteriophages interact also directly with epithelium through adhesion to mucus or through specifically biding to cellular receptors (endocytosis) and non-specific binding to membrane vesicles (transcytosis). Bacteriophage-epithelium uptake protects the cells from bacterial invasion and proliferation and enables the delivery of bacteriophage nucleic acids (HGT) and proteins into the nucleus. (B) Asthmatic epithelium is characterized by Goblet hyperplasia, mucus hypersecretion, MCC impairment and disrupted TJs that lead to bacterial adherence and invasion into the human cells or access of bacteria into the lamina paracellularly. In the case of asthma, bacteriophage communities are deregulated, as it is presented in the figure, and this may be associated with an altered microbiota profile with limited bacterial diversity and dominance of specific bacterial species. The role of prophage elements in bacterial genomes has also an influence on the ability of pathogens to provoke infection and epithelial damage. Irritated asthmatic epithelium secretes a range of chemokines and cytokines, contributing to immune system activation and chronic inflammation in asthma. The image was created using BioRender.