Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma

D. S. Ferreira; R. Annoni; L. F. F. Silva; M. Buttignol; A. B. G. Santos; M. C. R. Medeiros; L. N. S. Andrade; C. Y. Yick; P. J. Sterk; J. L. M. Sampaio; M. Dolhnikoff; S. E. Wenzel; T. Mauad

doi:https://doi.org/10.1111/j.1365-2222.2012.04047.x

Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma

D. S. Ferreira, R. Annoni, L. F. F. Silva, M. Buttignol, A. B. G. Santos, M. C. R. Medeiros, L. N. S. Andrade, C. Y. Yick, P. J. Sterk, J. L. M. Sampaio, M. Dolhnikoff, S. E. Wenzel, T. Mauad

Research output: Contribution to journal › Article › Academic › peer-review

48 Citations (Scopus)

Abstract

Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) 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 TLR2, TLR3, TLR4 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 Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 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 (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). 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 TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 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 TLR3 expression in the outer layer of large airways and greater TLR4 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 DCtrls. MA and HCtrls had only a small difference in TLR3 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

Original language	English
Pages (from-to)	1459-1471
Journal	Clinical and experimental allergy
Volume	42
Issue number	10
DOIs	https://doi.org/10.1111/j.1365-2222.2012.04047.x
Publication status	Published - 2012

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Ferreira, D. S., Annoni, 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. (2012). Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma. Clinical and experimental allergy, 42(10), 1459-1471. https://doi.org/10.1111/j.1365-2222.2012.04047.x

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title = "Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma",

abstract = "Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) 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 TLR2, TLR3, TLR4 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 Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 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 (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). 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 TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 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 TLR3 expression in the outer layer of large airways and greater TLR4 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 DCtrls. MA and HCtrls had only a small difference in TLR3 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",

author = "Ferreira, {D. S.} and R. Annoni and Silva, {L. F. F.} and M. Buttignol and Santos, {A. B. G.} and Medeiros, {M. C. R.} and Andrade, {L. N. S.} and Yick, {C. Y.} and Sterk, {P. J.} and Sampaio, {J. L. M.} and M. Dolhnikoff and Wenzel, {S. E.} and T. Mauad",

year = "2012",

doi = "https://doi.org/10.1111/j.1365-2222.2012.04047.x",

language = "English",

volume = "42",

pages = "1459--1471",

journal = "Clinical and experimental allergy",

issn = "0954-7894",

publisher = "Wiley-Blackwell",

number = "10",

}

Ferreira, DS, Annoni, R, Silva, LFF, Buttignol, M, Santos, ABG, Medeiros, MCR, Andrade, LNS, Yick, CY, Sterk, PJ, Sampaio, JLM, Dolhnikoff, M, Wenzel, SE & Mauad, T 2012, 'Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma', Clinical and experimental allergy, vol. 42, no. 10, pp. 1459-1471. https://doi.org/10.1111/j.1365-2222.2012.04047.x

TY - JOUR

T1 - Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma

AU - Ferreira, D. S.

AU - Annoni, R.

AU - Silva, L. F. F.

AU - Buttignol, M.

AU - Santos, A. B. G.

AU - Medeiros, M. C. R.

AU - Andrade, L. N. S.

AU - Yick, C. Y.

AU - Sterk, P. J.

AU - Sampaio, J. L. M.

AU - Dolhnikoff, M.

AU - Wenzel, S. E.

AU - Mauad, T.

PY - 2012

Y1 - 2012

N2 - Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) 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 TLR2, TLR3, TLR4 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 Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 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 (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). 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 TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 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 TLR3 expression in the outer layer of large airways and greater TLR4 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 DCtrls. MA and HCtrls had only a small difference in TLR3 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

AB - Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) 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 TLR2, TLR3, TLR4 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 Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 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 (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). 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 TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 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 TLR3 expression in the outer layer of large airways and greater TLR4 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 DCtrls. MA and HCtrls had only a small difference in TLR3 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

U2 - https://doi.org/10.1111/j.1365-2222.2012.04047.x

DO - https://doi.org/10.1111/j.1365-2222.2012.04047.x

M3 - Article

C2 - 22994343

SN - 0954-7894

VL - 42

SP - 1459

EP - 1471

JO - Clinical and experimental allergy

JF - Clinical and experimental allergy

IS - 10

ER -