Skin Commensals Amplify the Innate Immune Response to Pathogens by Activation of Distinct Signaling Pathways
Skin Commensals Amplify the Innate Immune Response to Pathogens by Activation of Distinct Signaling Pathways
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DOI：
10.1038/jid.2010.328
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发表时间：
2011-02-01
影响因子：
6.5
通讯作者：
Schittek, Birgit
中科院分区：
文献类型：
--
作者：
Wanke, Ines;Steffen, Heiko;Schittek, Birgit
关于不同微生物信号对皮肤屏障器官功能的影响以及常驻微生物菌群和病原微生物之间的相互依赖性知之甚少。这项研究表明，葡萄球菌和致病性葡萄球菌在诱导抗菌肽/蛋白（AMP）表达和激活人类原代角质形成细胞中不同信号通路的能力不同。皮肤表皮细胞的分泌因子通过Toll样受体（TLR）-2、EGFR和NF-κ B激活诱导原代人角质形成细胞中AMP HBD-3和RNase 7的表达，而致病性葡萄球菌的分泌因子激活丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶/AKT信号通路并抑制NF-κ B激活。有趣的是，大肠杆菌能够通过增加AMP表达的诱导和废除NF-κ B抑制来放大人角质形成细胞对病原体的先天免疫应答，这表明两种激活途径可以以协同方式起作用。这些数据表明，真菌和病原微生物进化出特定的机制来调节皮肤的先天免疫。
Little is known about the impact of different microbial signals on skin barrier organ function and the interdependency between resident microflora and pathogenic microorganisms. This study shows that commensal and pathogenic staphylococci differ in their ability to induce expression of antimicrobial peptides/proteins (AMPs) and activate different signaling pathways in human primary keratinocytes. Whereas secreted factors of skin commensals induce expression of the AMPs HBD-3 and RNase7 in primary human keratinocytes via Toll-like receptor (TLR)-2, EGFR, and NF-kappa B activation, those of pathogenic staphylococci activate the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT signaling pathways and suppress NF-kappa B activation. Interestingly, commensal bacteria are able to amplify the innate immune response of human keratinocytes to pathogens by increased induction of AMP expression and abrogation of NF-kappa B suppression, suggesting that the two activation pathways can act in a synergistic way. These data indicate that commensal and pathogenic microorganisms evolved specific mechanisms to modulate innate immunity of the skin.