Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, Colorado, USA.
Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, Colorado, USA; Department of Pediatrics, University of Colorado Denver, 13065 East 17th Avenue, Aurora, Colorado, USA.
J Invest Dermatol. 2019 Aug;139(8):1753-1761.e4. doi: 10.1016/j.jid.2019.02.006. Epub 2019 Feb 16.
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.
金黄色葡萄球菌是一种重要的细菌病原体，它可以穿透屏障进入皮肤的表皮和真皮。我们假设金黄色葡萄球菌细胞壁产物脂磷壁酸（LTA）可能导致炎症和皮肤屏障缺陷的发展；然而，LTA 在体内的作用尚未得到很好的理解。在这项研究中，我们研究了真皮内金黄色葡萄球菌 LTA 诱导的作用。我们发现 LTA 处理的皮肤中的角质形成细胞高度增殖，Ki67 表达增加了 10 倍。此外，我们观察到 LTA 导致皮肤屏障损伤，丝聚蛋白和兜甲蛋白表达大量减少。此外，IL-1 家族炎症细胞因子以及中性粒细胞趋化因子 Cxcl1 和 Cxcl2 的水平也升高了。同时，我们观察到大量中性粒细胞浸润到表皮中。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 拮抗剂减轻了 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。总之，我们表明金黄色葡萄球菌 LTA 本身足以促进角质形成细胞增殖、抑制表皮屏障蛋白的表达、诱导 IL-1 信号转导，并募集参与皮肤炎症的细胞。
