Journal
ALLERGY
Volume 64, Issue 11, Pages 1580-1587Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1398-9995.2009.02050.x
Keywords
atopic dermatitis; human; macrophages; TLR-2
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Funding
- Deutsche Dermatologische Gesellschaft (DDG)
- [DFG-SFB566-A6]
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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-1 beta after stimulation with TLR-2 ligands. Conclusion: 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.
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