Phenol-soluble modulins α are major virulence factors of Staphylococcus aureus secretome promoting inflammatory response in human epidermis.
Phenol-soluble modulins α are major virulence factors of Staphylococcus aureus secretome promoting inflammatory response in human epidermis.
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DOI：
10.1080/21505594.2021.1975909
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Bodet C
中科院分区：
文献类型：
--
作者：
Damour A;Robin B;Deroche L;Broutin L;Bellin N;Verdon J;Lina G;Leclère FM;Garcia M;Cremniter J;Lévêque N;Bodet C
金黄色葡萄球菌是一种常见于健康人群的皮肤微生物。然而，S.金黄色葡萄球菌也可引起皮肤感染，并导致炎性皮肤病如特应性皮炎（AD）的突然发作，其特征在于皮肤微生物群与S.金黄色葡萄球菌为优势种。然而，这种病原体的主要毒力因子，如苯酚可溶性调节蛋白（PSM）毒素在表皮炎症中的作用仍然知之甚少。用亚裂解浓度的合成和纯化PSM α3刺激原代人角质形成细胞，导致大量促炎趋化因子和细胞因子基因表达上调，包括CXCL 1、CXCL 2、CXCL 3、CXCL 5、CXCL 8、CCL 20、IL-1α、IL-1β、IL-6、IL-36γ和TNF-α，同时诱导CXCL 8、CCL 20、TNF-α和IL-6的释放。此外，利用S.结果表明，PSM是S. aureus的主要因子。负责人角质形成细胞中促炎介质诱导的金黄色葡萄球菌分泌蛋白。另一方面，在人皮肤外植体的离体模型（一种多层表皮的生理学相关模型）的局部和基底层刺激期间，含α型PSM的上清液引发促炎介质表达和分泌的强烈诱导。综上所述，本研究结果表明，PSM，更具体地说，α型PSM是S.金黄色葡萄球菌在人表皮感染期间诱导有效的炎症反应，从而可能通过皮肤炎症的恶化导致AD发作。
Staphylococcus aureus is a skin commensal microorganism commonly colonizing healthy humans. Nevertheless, S. aureus can also be responsible for cutaneous infections and contribute to flare-up of inflammatory skin diseases such as atopic dermatitis (AD), which is characterized by dysbiosis of the skin microbiota with S. aureus as the predominant species. However, the role of major virulence factors of this pathogen such as phenol-soluble modulin (PSM) toxins in epidermal inflammation remains poorly understood. Stimulation of primary human keratinocytes with sublytic concentrations of synthetic and purified PSM α3 resulted in upregulation of a large panel of pro-inflammatory chemokine and cytokine gene expression, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL8, CCL20, IL-1α, IL-1β, IL-6, IL-36γ and TNF-α, while inducing the release of CXCL8, CCL20, TNF-α and IL-6. In addition, using S. aureus culture supernatant from mutants deleted from genes encoding either α-type PSMs or all PSM production, PSMs were shown to be the main factors of S. aureus secretome responsible for pro-inflammatory mediator induction in human keratinocytes. On the other hand, α-type PSM-containing supernatant triggered an intense induction of pro-inflammatory mediator expression and secretion during both topical and basal layer stimulation of an ex vivo model of human skin explants, a physiologically relevant model of pluristratified epidermis. Taken together, the results of this study show that PSMs and more specifically α-type PSMs are major virulence factors of S. aureus inducing a potent inflammatory response during infection of the human epidermis and could thereby contribute to AD flare-up through exacerbation of skin inflammation.
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