Mapping of TLR5 and TLR7 in central and distal human airways and identification of reduced TLR expression in severe asthma.
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.
Department of Experimental Medical Science, Lund University, Lund, Sweden.
M M
MM
Shikhagaie
C K
CK
Andersson
M
M
Mori
I
I
Kortekaas Krohn
A
A
Bergqvist
R
R
Dahl
E
E
Ekblad
H J
HJ
Hoffmann
L
L
Bjermer
J S
JS
Erjefält
D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis* / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis* / Q000276:immunology
C495346:TLR5 protein, human; C495348:TLR7 protein, human; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7
TLR5; TLR7; asthma; severe asthma