Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism
Article first published online: 25 APR 2008
© 2008 The Authors
Volume 63, Issue 6, pages 728–734, June 2008
How to Cite
Niebuhr, M., Langnickel, J., Draing, C., Renz, H., Kapp, A. and Werfel, T. (2008), Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism. Allergy, 63: 728–734. doi: 10.1111/j.1398-9995.2008.01721.x
- Issue published online: 25 APR 2008
- Article first published online: 25 APR 2008
- Accepted for publication 19 February 2008
- atopic dermatitis;
- lipoteichoic acid;
- 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.