Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.
Cell Rep. 2023 Oct 31;42(10):113148. doi: 10.1016/j.celrep.2023.113148. Epub 2023 Sep 19.
Staphylococcus aureus is the most common cause of bacterial skin infections in humans, including patients with atopic dermatitis (AD). Polymorphonuclear neutrophils (PMNs) are the first cells to infiltrate an infection site, where they usually provide an effective first line of defense, including neutrophil extracellular trap (NET) formation. Here, we show that infiltrating PMNs in inflamed human and mouse skin enhance S. aureus skin colonization and persistence. Mechanistically, we demonstrate that a crosstalk between keratinocytes and PMNs results in enhanced NET formation upon S. aureus infection, which in turn induces oxidative stress and expression of danger-associated molecular patterns such as high-mobility-group-protein B1 (HMGB1) in keratinocytes. In turn, HMGB1 enhances S. aureus skin colonization and persistence by promoting skin barrier dysfunctions by the downregulation of epidermal barrier genes. Using patient material, we show that patients with AD exhibit enhanced presence of PMNs, NETs, and HMGB1 in the skin, demonstrating the clinical relevance of our finding.
金黄色葡萄球菌是人类细菌性皮肤感染最常见的原因，包括特应性皮炎（AD）患者。多形核粒细胞（PMN）是第一个浸润感染部位的细胞，它们通常提供有效的第一道防线，包括中性粒细胞胞外陷阱（NET）的形成。在这里，我们表明，在发炎的人类和小鼠皮肤中浸润的 PMN 增强了金黄色葡萄球菌的皮肤定植和持续存在。从机制上讲，我们证明了角质形成细胞和 PMN 之间的串扰导致金黄色葡萄球菌感染后 NET 形成增强，进而诱导角质形成细胞中氧化应激和危险相关分子模式（如高迁移率族蛋白 B1（HMGB1））的表达。反过来，HMGB1 通过下调表皮屏障基因促进皮肤屏障功能障碍，从而增强金黄色葡萄球菌的皮肤定植和持续存在。使用患者材料，我们表明 AD 患者的皮肤中存在更多的 PMN、NET 和 HMGB1，这表明了我们发现的临床相关性。
