BACKGROUND: The toll-like receptors, TLR5 and TLR7, have recently been proposed in asthma immunopathogenesis. While supporting data come from animal or in vitro studies, little is known about TLR5 and TLR7 expression in human asthmatic airways. METHODS: Advanced immunohistochemical mapping of TLR5 and TLR7 was performed on bronchial and transbronchial biopsies from healthy individuals and patients with moderate and severe asthma. RESULTS: TLR5 was identified in multiple structural cells; bronchial epithelium, alveolar type II pneumocytes, plasma cells, macrophages and neutrophils. Contrary to bronchial TLR5, which had a basolateral expression, alveolar TLR5 had polarized apical localization. Patients with severe asthma had decreased total and epithelial TLR5 expression compared to controls and moderate asthmatics (P < 0.001). TLR7 expression was found in several structural cells and asthma-related immune cells. Whereas TLR7 expression was decreased in severe asthmatics (P < 0.001), nerve-associated TLR7 increased (P = 0.035). Within the asthma groups, both TLR5 and TLR7 expression correlated with multiple lung function parameters. CONCLUSIONS: Our results reveal broad expression patterns of TLR5 and TLR7 in the lung and that the expression is decreased in severe asthma. Hence, severe asthmatics may suffer from insufficient TLR signalling during viral or bacterial infections leading to poor and impaired defence mechanisms.
BACKGROUND: The toll-like receptors, TLR5 and TLR7, have recently been proposed in asthma immunopathogenesis. While supporting data come from animal or in vitro studies, little is known about TLR5 and TLR7 expression in human asthmatic airways. METHODS: Advanced immunohistochemical mapping of TLR5 and TLR7 was performed on bronchial and transbronchial biopsies from healthy individuals and patients with moderate and severe asthma. RESULTS:TLR5 was identified in multiple structural cells; bronchial epithelium, alveolar type II pneumocytes, plasma cells, macrophages and neutrophils. Contrary to bronchial TLR5, which had a basolateral expression, alveolar TLR5 had polarized apical localization. Patients with severe asthma had decreased total and epithelial TLR5 expression compared to controls and moderate asthmatics (P < 0.001). TLR7 expression was found in several structural cells and asthma-related immune cells. Whereas TLR7 expression was decreased in severe asthmatics (P < 0.001), nerve-associated TLR7 increased (P = 0.035). Within the asthma groups, both TLR5 and TLR7 expression correlated with multiple lung function parameters. CONCLUSIONS: Our results reveal broad expression patterns of TLR5 and TLR7 in the lung and that the expression is decreased in severe asthma. Hence, severe asthmatics may suffer from insufficient TLR signalling during viral or bacterial infections leading to poor and impaired defence mechanisms.
Authors: J A Tuazon; B Kilburg-Basnyat; L M Oldfield; R Wiscovitch-Russo; K Dunigan-Russell; A V Fedulov; K J Oestreich; K M Gowdy Journal: Curr Allergy Asthma Rep Date: 2022-04-08 Impact factor: 4.919
Authors: Luke Hatchwell; Adam Collison; Jason Girkin; Kristy Parsons; Junyao Li; Jie Zhang; Simon Phipps; Darryl Knight; Nathan W Bartlett; Sebastian L Johnston; Paul S Foster; Peter A B Wark; Joerg Mattes Journal: Thorax Date: 2015-06-24 Impact factor: 9.139
Authors: Hitasha Rupani; Rocio T Martinez-Nunez; Patrick Dennison; Laurie C K Lau; Nivenka Jayasekera; Tom Havelock; Ana S Francisco-Garcia; Christopher Grainge; Peter H Howarth; Tilman Sanchez-Elsner Journal: Am J Respir Crit Care Med Date: 2016-07-01 Impact factor: 21.405