Respiratory microbiome and epithelial interactions shape immunity in the lungs

Abstract

The airway epithelium represents a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli including microbes and allergens. However, lung epithelial cells are increasingly recognized as active effectors of microbial defence, contributing to both innate and adaptive immune function in the lower respiratory tract. These cells express an ample repertoire of pattern recognition receptors with specificity for conserved microbial and host motifs. Modern molecular techniques have uncovered the complexity of the lower respiratory tract microbiome. The interaction between the microbiota and the airway epithelium is key to understanding how stable immune homeostasis is maintained. Loss of epithelial integrity following exposure to infection can result in the onset of inflammation in susceptible individuals and may culminate in lung disease. Here we discuss the current knowledge regarding the molecular and cellular mechanisms by which the pulmonary epithelium interacts with the lung microbiome in shaping immunity in the lung. Specifically, we focus on the interactions between the lung microbiome and the cells of the conducting airways in modulating immune cell regulation, and how defects in barrier structure and function may culminate in lung disease. Understanding these interactions is fundamental in the search for more effective therapies for respiratory diseases.

Keywords: immunity; lungs; mucosal immunology; respiratory epithelium; respiratory microbiome.

Figure 1

Composition of the respiratory epithelium in health. The human respiratory tract is divided into the upper respiratory tract including the nasal cavity, pharynx, larynx, and the lower respiratory tract that comprises the conducting airways (trachea and bronchi), the small airways (bronchioles) and the respiratory zone (the alveoli). The trachea and large airways are composed of ciliated cells, mucus‐secreting goblet cells, neuroendocrine cells and undifferentiated basal cells. Stromal cells including fibroblasts provide extracellular matrix that modulate airway epithelial cell turnover. The alveoli are comprised of alveolar macrophages and alveolar type I and type II cells.

Figure 2

Response of the airway epithelium to infection. Bacteria and viruses bind to cellular receptors, including intercellular adhesion molecule 1 (ICAM‐1), sialic acid residues, platelet‐activating factor (PAF) and mannose‐6‐phosphate (Man‐6‐P). The pathogens are internalized in airway epithelial cells, which induces the production of innate immune defensins and the stimulation of intracellular and extracellular immune receptors such as the toll‐like receptors (TLR), retinoic acid‐inducible gene‐I‐like receptor (RLRs) and NOD‐like receptors (NLRs). In healthy individuals, pathogen clearance is achieved following the generation of pro‐inflammatory innate and adaptive immune responses.