Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation
Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation
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DOI：
10.1128/iai.00401-15
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发表时间：
2015-09-01
影响因子：
3.1
通讯作者：
Kahlenberg, J. Michelle
中科院分区：
文献类型：
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作者：
Syed, Adnan K.;Reed, Tamra J.;Kahlenberg, J. Michelle
金黄色葡萄球菌是一种寄生在皮肤上的人类细菌。虽然它通常是无害的，但它与特应性皮炎发病机制有很强的联系，并已成为美国皮肤和软组织感染的主要原因。决定S.金黄色葡萄球菌的致病性仍在确定中。在这项工作中，我们利用原代角质形成细胞培养和表皮小鼠定植模型来研究S。金黄色葡萄球菌酚可溶性调节蛋白（PSM）在促炎细胞因子释放和炎症诱导中的作用。我们证明了许多种葡萄球菌都能引起角质形成细胞释放白细胞介素18（IL-18），而S。金黄色葡萄球菌PSM是刺激IL-18从角质形成细胞释放所必需的，并且足以独立于半胱天冬酶1。此外，在表皮暴露于野生型S.金黄色葡萄球菌，而不是S.在金黄色葡萄球菌Delta psm中，我们看到了大体病理学的显著变化，以及促炎细胞因子的全身释放。这项工作证明了PSM肽在S.金黄色葡萄球菌介导的炎性细胞因子从体外和体内角质形成细胞释放，并进一步暗示PSM作为重要的致病因素。
Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis and has become the leading cause of skin and soft tissue infections in the United States. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol-soluble modulins (PSMs) in proinflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of interleukin 18 (IL-18) from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independently of caspase 1. Further, after 7 days of epicutaneous exposure to wild-type S. aureus, but not S. aureus Delta psm, we saw dramatic changes in gross pathology, as well as systemic release of proinflammatory cytokines. This work demonstrates the importance of PSM peptides in S. aureus-mediated inflammatory cytokine release from keratinocytes in vitro and in vivo and further implicates PSMs as important contributors to pathogenesis.