title: Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism.
abstract: BACKGROUND
  Atopic dermatitis (AD) is often complicated by an enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. Toll-like receptors (TLR), especially TLR-2 recognizes cell wall components of S. aureus, e.g. lipoteichoic acid (LTA) and peptidoglycan (PGN). A heterozygous TLR-2 R753Q polymorphism occurs in a frequency of 11.5% in adult AD patients and has been shown to be associated with a severe phenotype of AD.
  
  
  METHODS
  The aim of this study was to investigate the impact of TLR-2 agonists (LTA, PGN and Pam3Cys) on cytokine production in human monocytes from AD patients with the TLR-2 R753Q polymorphism compared with that of AD patients with 'wild type' TLR-2 and control individuals to elucidate the functional role of the TLR-2 R753Q polymorphism.
  
  
  RESULTS
  Monocytes from AD patients with the TLR-2 R753Q mutation produced significantly more IL-6 and IL-12 compared with that of AD patients with nonmutated TLR-2 upon stimulation with TLR-2 agonists.
  
  
  CONCLUSIONS
  We show for the first time functional differences in TLR-2 responsiveness of monocytes from AD patients with the TLR-2 R753Q mutation compared with wild type AD patients in a ligand-dependent manner.
  
  
  CONCLUSIONS
  Our data support the emerging concept that AD patients have a dysbalance in innate and acquired immunity. TLR-2 may be essential in the pathogenesis and maintenance of AD and may be involved in the enhanced susceptibility to skin infections with S. aureus and in a higher inflammatory response in patients with AD carrying the TLR-2 polymorphism.
authors.affiliation: Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Niebuhr
authors.forename: J
authors.initials: J
authors.lastname: Langnickel
authors.forename: C
authors.initials: C
authors.lastname: Draing
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: T
authors.initials: T
authors.lastname: Werfel
mesh_terms: D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; C009900:lipoteichoic acid