Journal Article

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

Delong Jiao Chun-Kwok Wong Huai-Na Qiu Jie Dong Zhe Cai Man Chu Kam-Lun Hon Miranda Sin-Man Tsang Christopher Wai-Kei Lam

2016

Overview

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Antibodies / Atopic dermatitis / Basophils - immunology / Biomedical and Life Sciences / Biomedicine / Cell activation / Cell adhesion / Cell culture / Cell Proliferation / Chemokines / Chemokines - metabolism / Coculture Techniques / Cytokines / Dermatitis / Dermatitis, Atopic - immunology / Dermatitis, Atopic - microbiology / Dermatitis, Atopic - pathology / Eczema / Eosinophils - immunology / Extracellular signal-regulated kinase / Female / Fibroblasts / Fibroblasts - metabolism / Fibroblasts - pathology / Humans / Immunology / Inflammation / Inflammation - pathology / Intercellular adhesion molecule 1 / Intercellular Adhesion Molecule-1 - metabolism / Kinases / Leukocytes (basophilic) / Leukocytes (eosinophilic) / Ligands / MAP kinase / MAP Kinase Signaling System / Medical Microbiology / Mice, Inbred BALB C / Microbiology / Models, Biological / NF-kappa B - metabolism / NF-κB protein / NOD2 protein / Nod2 Signaling Adaptor Protein - metabolism / Oligomerization / p38丝裂原活化蛋白激酶 / Pattern recognition receptors / Protein kinase / research-article / Signal Transduction / Skin - pathology / Skin diseases / Skin lesions / Staphylococcus aureus / Staphylococcus aureus - physiology / TLR2 protein / Toll-Like Receptor 2 - metabolism / Toll-like receptors / Vaccine / 嗜碱性 / 嗜酸性粒细胞 / 皮肤成纤维细胞 / 皮肤炎症 / 相互作用 / 配体 / 金黄色葡萄球菌