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 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.
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-2R753Q polymorphism occurs in a frequency of 11.5% in adult ADpatients 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 ADpatients with the TLR-2R753Q polymorphism compared with that of ADpatients with 'wild type' TLR-2 and control individuals to elucidate the functional role of the TLR-2R753Q polymorphism. RESULTS: Monocytes from ADpatients with the TLR-2R753Q mutation produced significantly more IL-6 and IL-12 compared with that of ADpatients 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 ADpatients with the TLR-2R753Q mutation compared with wild type ADpatients in a ligand-dependent manner. CLINICAL IMPLICATION: Our data support the emerging concept that ADpatients 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: Susanne Hradetzky; Lennart M Roesner; Hari Balaji; Annice Heratizadeh; Irene Mittermann; Rudolf Valenta; Thomas Werfel Journal: J Invest Dermatol Date: 2014-01-17 Impact factor: 8.551
Authors: Marco A Quevedo-Diaz; Chang Song; Yanbao Xiong; Haiyan Chen; Larry M Wahl; Suzana Radulovic; Andrei E Medvedev Journal: J Leukoc Biol Date: 2010-07-08 Impact factor: 4.962