Mechanisms how mucosal innate immunity affects progression of allergic airway disease.

INTRODUCTION: Activation of antigen-independent inflammation (a.k.a. the 'innate' immune response (IIR)) plays a complex role in allergic asthma (AA). Although activation of the pulmonary IIR by aerosolized bacterial lipopolysaccharide early in life may be protective of AA, respiratory viral infections promote AA. The mechanisms how the mucosal IIR promotes allergic sensitization, remodeling, and altered epithelial signaling are not understood. Areas covered: This manuscript overviews: 1. Mechanistic studies identifying how allergens and viral patterns activate the mucosal IIR; 2. Research that reveals a major role played by specialized epithelial cells in the bronchiolar-alveolar junction in triggering inflammation and remodeling; 3. Reports linking the mucosal IIR with epithelial cell-state change and barrier disruption; and, 4. Observations relating mesenchymal transition with the expansion of the myofibroblast population. Expert commentary: Luminal allergens and viruses activate TLR signaling in key sentinel cells producing epithelial cell state transition, disrupting epithelial barrier function, and expanding the pulmonary myofibroblast population. These signals are transduced through a common NFκB/RelA -bromodomain containing four (BRD4) pathway, an epigenetic remodeling complex reprogramming the genome. Through this pathway, the mucosal IIR is a major modifier of adaptive immunity, AA and acute exacerbation-induced remodeling.