‘Farm dust extract increases the epithelial barrier function of human bronchial epithelial cells partly via MyD88 signalling’

Abstract

Abstract Epidemiological studies showed that farmer’s children have a lower incidence of childhood asthma, which was partly attributed to a higher microbial exposure. Recently, distorted airway epithelium is considered an active player in pathogenesis of asthma. Interestingly, Toll-like receptor (TLR) ligation in the gut was found to enhance the gut epithelial barrier function. We hypothesize that exposure of the airways to microbial-rich farm dust may have barrier-enhancing effects on the airway epithelium and thereby may contribute to the protection against asthma in farmer’s children. In this study, the effect of farm dust extracts (FDE) collected from traditional German farms was investigated on barrier function and -repair in primary bronchial epithelial cells (PBECs). The expression of tight (TJs) and adherens junctions (AJs)-important to maintain the barrier function- and the involvement of TLR-induced MyD88 signalling were investigated. FDE exposure induced a dose-dependent two-fold increase in resistance measured by ECIS and up to 70% reduction in permeability in undifferentiated PBECs. Furthermore, restoration of barrier function of fully differentiated PBECs after cigarette smoke exposure was accelerated in the presence of FDE. The increase in barrier function was accompanied by an 1.5 to 2-fold enhanced mRNA expression of TJs occludin-1, claudin-1 and −4 and AJ E-cadherin. In search for the underlying mechanisms, we found that the increased barrier resistance could be significantly attenuated by blocking MyD88 signalling. These data altogether suggest that FDE exposure strengthen the epithelial barrier function partly via MyD88 signalling and, thereby, possibly reduce the risk of development of asthma and allergies.