Chronic oxidative injury triggers epigenetic reprogramming of the lung epithelial barrier known as 'epithelial-mesenchymal transition' (EMT), as part of the mucosal repair response mediated by the cytokine TGF-β. In Nature Microbiology, Brasier and colleagues show that EMT silences the production of protective type I and type III interferons and promotes enhanced viral replication in epithelial cells during infection with rhinovirus or respiratory syncytial virus. In human small-airway epithelial cells, EMT is associated with diminished expression of the transcription factor IRF1 and less binding of IRF1 and IRF7 to the promoters of IFNB1 and IFNL1 (which encode interferons). TGF-β-driven EMT induces upregulation of the transcription factor ZEB1, which represses IRF1 by inducing the accumulation of repressive epigenetic marks and decreases the expression of IFNB1 and IFNL1. These observations provide a mechanistic basis for the observation that asthma is associated with enhanced susceptibility to pulmonary infection.

Nat. Microbiol. (5 June 2017) doi:10.1038/nmicrobiol.2017.86