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Keywords:

  • atopic dermatitis;
  • human;
  • lipoteichoic acid;
  • monocytes;
  • Pam3Cys;
  • peptidoglycan;
  • toll-like receptor 2

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.

Conclusion:  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.

Clinical implication:  Our data support the emerging concept that AD patients have a dysbalance in innate and aquired 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.