Impairment of respiratory host defence resulting from cigarette smoke-induced changes in airway epithelial cell differentiation

Cigarette smoking (CS) is known to increase susceptibility to respiratory tract infections and alter differentiation of airway epithelial cells. Host defence proteins (HDPs) are key mediators of mucosal host defence. We hypothesized that CS-induced alterations in epithelial differentiation result in a decrease in constitutively expressed HDPs, thus rendering the host more susceptible to infection. Primary bronchial epithelial cells (PBEC) were cultured at the air-liquid interface (ALI) and during differentiation daily exposed to whole CS. Gene expression and protein levels of HDPs and epithelial cell-specific markers were subsequently assessed, and host defence activities were tested. CS-exposure of differentiating PBEC up to 19 days resulted in impaired epithelial differentiation and a reduction in luminal cell-specific HDP expression (i.e. SLPI, pIgR and short/long PLUNC) compared to controls. This was partly restored upon cessation of CS exposure. This reduced expression was accompanied by a significantly decreased trans-epithelial transport of dimeric IgA (~75% reduction) and a reduced killing of M. catarrhalis. Whether and how these changes affect airway microbiome composition is currently under investigation. These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and COPD patients to respiratory infections.This work was s...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Cell Biology and Immunopathology Source Type: research