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
  Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.
authors.affiliation: Department of Pathology, São Paulo University Medical School, São Paulo, Brazil. dioferreira@yahoo.com.br
authors.forename: D S
authors.initials: DS
authors.lastname: Ferreira
authors.forename: R
authors.initials: R
authors.lastname: Annoni
authors.forename: L F F
authors.initials: LF
authors.lastname: Silva
authors.forename: M
authors.initials: M
authors.lastname: Buttignol
authors.forename: A B G
authors.initials: AB
authors.lastname: Santos
authors.forename: M C R
authors.initials: MC
authors.lastname: Medeiros
authors.forename: L N S
authors.initials: LN
authors.lastname: Andrade
authors.forename: C Y
authors.initials: CY
authors.lastname: Yick
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: J L M
authors.initials: JL
authors.lastname: Sampaio
authors.forename: M
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: S E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: T
authors.initials: T
authors.lastname: Mauad
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000401:mortality*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D000094632:Thymic Stromal Lymphopoietin