title: Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis.
abstract: BACKGROUND
  In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. The pattern recognition receptor toll-like receptor (TLR)-2 recognizes components of S. aureus, for example, lipoteichoic acid (LTA) and peptidoglycan (PGN) and, therefore, might be crucial in the pathogenesis and flare-ups of AD.
  
  
  OBJECTIVE
  To investigate TLR-2 expression and cytokine secretion in macrophages from patients with AD compared to healthy controls upon TLR-2 stimulation with PGN, LTA and Pam3Cys.
  
  
  METHODS
  Macrophages were cultivated from highly purified peripheral blood monocytes of AD patients and nonatopic healthy controls and stimulated with PGN, LTA and Pam3Cys in a time and dose-dependent manner. Afterwards, TLR-2 expression and cytokine secretion were measured on protein and mRNA level. TLR-1 and TLR-6 expression were investigated on the mRNA level. Immunohistochemical stainings from punch biopsies were performed to investigate TLR-2 expression in skin macrophages.
  
  
  RESULTS
  We could clearly show that macrophages from patients with AD expressed significantly less TLR-2, whereas the expression pattern of TLR-1 and TLR-6 were not altered. Macrophages had a reduced capacity to produce pro-inflammatory cytokines such as IL-6, IL-8 and IL-1beta after stimulation with TLR-2 ligands.
  
  
  CONCLUSIONS
  Our findings clearly show an impaired TLR-2 expression and functional differences of TLR-2-mediated effects on macrophages of AD patients compared to healthy controls which might contribute to the enhanced susceptibility to skin infections with S. aureus in AD.
authors.affiliation: Department of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Niebuhr
authors.forename: C
authors.initials: C
authors.lastname: Lutat
authors.forename: S
authors.initials: S
authors.lastname: Sigel
authors.forename: T
authors.initials: T
authors.lastname: Werfel
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid