Staphylococcus aureus-derived membrane vesicles exacerbate skin inflammation in atopic dermatitis
Staphylococcus aureus-derived membrane vesicles exacerbate skin inflammation in atopic dermatitis
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DOI：
10.1111/cea.12851
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发表时间：
2017-01-01
影响因子：
6.1
通讯作者：
Lee, J. C.
中科院分区：
文献类型：
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作者：
Jun, S. H.;Lee, J. H.;Lee, J. C.
背景：已知金黄色葡萄球菌的皮肤定植或感染可引发特应性皮炎（AD）的恶化。然而，金黄色葡萄球菌恶化AD的确切机制尚不清楚。目的探讨金黄色葡萄球菌源性膜囊泡（MVs）是否以及如何导致AD的恶化。方法采用免疫组化和免疫电镜检测AD病变表皮中葡萄球菌蛋白A （staphylococcal protein A， SPA）的表达。用金黄色葡萄球菌mv处理HaCaT细胞，分析细胞因子基因的表达。局部应用金黄色葡萄球菌mv治疗ad样皮肤病变后，分析了小鼠模型的免疫病理学和细胞因子基因谱。结果在金黄色葡萄球菌定植的AD病变表皮的角质形成细胞和细胞间隙中检测到MV成分SPA。来自金黄色葡萄球菌的完整mv将其成分递送到角质形成细胞并刺激促炎细胞因子基因的体外表达。使用小干扰rna敲除toll样受体2或核苷酸结合寡聚化结构域2可抑制白介素-8基因表达。在小鼠模型中，将完整的金黄色葡萄球菌mv局部应用于ad样皮肤病变，可诱导炎症细胞大量浸润并导致湿疹性皮炎。这种炎症反应与ad样皮肤病变中Th1/Th2混合免疫反应和趋化因子基因表达增强有关。结论及临床意义本研究显示金黄色葡萄球菌MVs在AD的众多外源性恶化因素中作为AD恶化的有效介质的重要性。因此，金黄色葡萄球菌mv可能被视为管理AD加重的治疗靶点之一。
BackgroundSkin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown.ObjectiveWe investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD.MethodsImmunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD-like skin lesions in a mouse model.ResultsThe MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro-inflammatory cytokine gene expression in vitro. A knock-down of Toll-like receptor 2 or nucleotide-binding oligomerization domain 2 using small interfering RNAs suppressed interleukin-8 gene expression. Topical application of intact S. aureus MVs to AD-like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD-like skin lesions.Conclusions and Clinical RelevanceThis study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.