Altered distribution patterns of TLR5 and TLR7 in the central airways of severe asthmatics

Abstract Toll-like receptors are a major class of pattern and damage recognition receptors controlling innate immune responses. TLR5 recognizes bacterial flagellin and TLR7 identifies single stranded viral RNA. The present study characterizes TLR5 and TLR7 expression pattern in central airways of asthmatics. Methods: Bronchial biopsies were obtained from healthy controls, uncontrolled asthmatics on inhaled glucocorticoids, and severe asthmatics on oral glucocorticoids. Subjects were classified according to GINA guidelines and asthma control score. Tissue sections were processed for immunohistochemical identification of TLR positive cells. Results: TLR5 immunoreactivity was identified in the airway epithelium, glands, smooth muscle, alveolar macrophages and plasma cells. In the airway epithelium, TLR5 had mainly a basolateral distribution. In severe asthmatics the overall and epithelial TLR5 immunoreactivity were significantly decreased. TLR7 displayed a distinct peri-nuclear expression. Quantification of the epithelial TLR7 immunoreactivity showed a significantly decreased expression in severe asthmatics compared to healthy controls and uncontrolled asthma. TLR7 expression was also detected in nerve cells, NK cells and mast cells. Conclusions: Our data suggest that patients with severe asthma have decreased expression of TLR5 and TLR7 compared to healthy controls and uncontrolled asthmatics. This altered expression may reflect a dysfunctional immune-regulation in severe asthmatics.