Department of Dermatology, Eberhard-Karls-University Tübingen, Tübingen, Germany.
J Invest Dermatol. 2011 Feb;131(2):382-90. doi: 10.1038/jid.2010.328. Epub 2010 Nov 4.
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-κB activation, those of pathogenic staphylococci activate the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT signaling pathways and suppress NF-κB 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-κB 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.
关于不同微生物信号对皮肤屏障器官功能的影响，以及常驻微生物群和病原微生物之间的相互依存关系，人们知之甚少。本研究表明，共生和病原性葡萄球菌在诱导人原代角质细胞表达抗菌肽/蛋白 (AMPs) 和激活不同信号通路的能力上存在差异。皮肤共生菌的分泌因子通过 Toll 样受体 (TLR)-2、EGFR 和 NF-κB 激活诱导人原代角质细胞中 AMPs HBD-3 和 RNase7 的表达，而病原性葡萄球菌的分泌因子则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-κB 激活。有趣的是，共生细菌能够通过增加 AMP 表达的诱导和 NF-κB 抑制的消除来增强人角质细胞对病原体的先天免疫反应，这表明这两个激活途径可以协同作用。这些数据表明，共生和病原微生物进化出了特定的机制来调节皮肤的先天免疫。
