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Toll‐like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma
Author(s) -
Ferreira D. S.,
Ani R.,
Silva L. F. F.,
Buttignol M.,
Santos A. B. G.,
Medeiros M. C. R.,
Andrade L. N. S.,
Yick C. Y.,
Sterk P. J.,
Sampaio J. L. M.,
Dolhnikoff M.,
Wenzel S. E.,
Mauad T.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04047.x
Subject(s) - thymic stromal lymphopoietin , medicine , immunology , asthma , inflammation , immune system , eosinophilic , airway , toll like receptor , receptor , innate immune system , pathology , surgery
Summary Background Airway inflammation in asthma involves innate immune responses. Toll‐like receptors ( TLR s) and thymic stromal lymphopoietin ( TSLP ) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated. Objective To analyse the expression of TLR 2, TLR 3, TLR 4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non‐smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with M ycoplasma pneumoniae and C hlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR 2, TLR 3, TLR 4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA , (13 non‐smokers, 11 smokers) and nine deceased control subjects ( DC trl). TLR s were also measured in 18 mild asthmatics ( MA ) and 12 healthy controls ( HC trl). M . pneumoniae and C . pneumoniae in autopsy lung tissue were analysed using real‐time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR 2 in the epithelial and outer layers of large and small airways compared with DC trls. Smoking asthmatics had lower TLR 2 levels in the inner and outer layers of the small airways than non‐smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA . FA patients had greater TLR 3 expression in the outer layer of large airways and greater TLR 4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA . No bacterial DNA was detected in FA or DC trls. MA and HC trls had only a small difference in TLR 3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.