Staphylococcus aureus Lipoteichoic Acid Damages the Skin Barrier through an IL-1-Mediated Pathway
Staphylococcus aureus Lipoteichoic Acid Damages the Skin Barrier through an IL-1-Mediated Pathway
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DOI：
10.1016/j.jid.2019.02.006
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发表时间：
2019-08-01
影响因子：
6.5
通讯作者：
Leung, Donald Y. M.
中科院分区：
文献类型：
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作者：
Brauweiler, Anne M.;Goleva, Elena;Leung, Donald Y. M.
金黄色葡萄球菌是一种重要的细菌病原体，可以穿透屏障进入皮肤的表皮和真皮。我们推测金黄色葡萄球菌细胞壁产物脂磷壁酸(LTA)可能有助于炎症和皮肤屏障缺陷的发展；然而，LTA在体内的作用尚不清楚。在这项研究中，我们研究了皮内金黄色葡萄球菌LTA诱导的效果。我们发现，LTA处理的皮肤角质形成细胞高度增殖，Ki67的表达水平增加了10倍。此外，我们观察到LTA对皮肤屏障造成了损害，丝状蛋白和氯化蛋白的表达大量丧失。此外，炎性细胞因子IL-1家族以及吸引中性粒细胞的趋化因子CXCL1和CxCL2的水平也增加。同时，我们观察到大量的中性粒细胞渗入表皮。最后，我们确定LTA诱导的信号部分是通过IL-1介导的，因为IL-1受体1型拮抗剂改善了LTA的作用，阻止了中性粒细胞的募集并增加了皮肤屏障蛋白的表达。综上所述，我们发现仅金黄色葡萄球菌LTA就足以促进角质形成细胞的增殖，抑制表皮屏障蛋白的表达，诱导IL-1信号转导，并招募参与皮肤炎症的细胞。
Staphylococcus aureus is a significant bacterial pathogen that may penetrate through the barrier into the epidermis and dermis of the skin. We hypothesized that the S. aureus cell wall product lipoteichoic acid (LTA) may contribute to the development of inflammation and skin barrier defects; however, the effects of LTA in vivo are not well understood. In this study, we examined the effects induced by intradermal S. aureus LTA. We found that keratinocytes in LTA-treated skin were highly proliferative, expressing 10-fold increased levels of Ki67. Furthermore, we observed that LTA caused damage to the skin barrier with substantial loss of filaggrin and loricrin expression. In addition, levels of the IL-1 family of inflammatory cytokines, as well as the neutrophil-attracting chemokines Cxcl1 and Cxcl2, were increased. Concomitantly, we observed significant numbers of neutrophils infiltrating into the epidermis. Finally, we determined that LTA-induced signals were mediated in part through IL-1, because an IL-1 receptor type 1 antagonist ameliorated the effects of LTA, blocking neutrophil recruitment and increasing the expression of skin barrier proteins. In summary, we show that S. aureus LTA alone is sufficient to promote keratinocyte proliferation, inhibit expression of epidermal barrier proteins, induce IL-1 signaling, and recruit cells involved in skin inflammation.