Department of Dermatology, University of Tübingen, Tübingen, Germany.
Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany.
Exp Dermatol. 2022 Mar;31(3):349-361. doi: 10.1111/exd.14478. Epub 2021 Oct 29.
Staphylococcus aureus colonization is abundant on the skin of atopic dermatitis (AD) patients where it contributes to skin inflammation. S. aureus produces virulence factors that distinguish it from commensal skin bacteria such as S. epidermidis and S. lugdunensis. However, it has remained unclear, which of these virulence factors have the strongest impact on AD. Membrane vesicles (MVs) are released by pathogenic bacteria and might play an essential role in the long-distance delivery of bacterial effectors such as virulence factors. We show that MVs are also released by skin commensals in a similar quantity and membrane lipid amount as those from pathogenic S. aureus. Interestingly, MVs from skin commensals can protect against S. aureus skin colonization by conditioning human skin for enhanced defence. In contrast, MVs released by S. aureus are able to induce CXCL8 and TNF-α in primary human keratinocytes, recruit neutrophils and induce neutrophil extracellular traps, which enhance S. aureus skin colonization. CXCL8 induction is TLR2- and NFkB-dependent and the induction level correlates with the membrane lipid and protein A content of the MVs. Interestingly, MVs of S. aureus strains from the lesional skin of AD patients show an enhanced membrane lipid and protein A content compared to the strains from the non-lesional sites and have an enhanced proinflammatory potential. Our data underline the complex interplay in host- and bacterial derived factors in S. aureus skin colonization and the important role of bacterial derived MVs and their membrane lipid and protein A content in skin inflammatory disorders.
金黄色葡萄球菌定植于特应性皮炎（AD）患者的皮肤，在皮肤炎症中起作用。金黄色葡萄球菌产生的毒力因子使其与表皮葡萄球菌和路邓葡萄球菌等共生皮肤细菌区分开来。然而，目前仍不清楚这些毒力因子中哪些对 AD 的影响最大。膜泡（MVs）由致病菌释放，可能在细菌效应物（如毒力因子）的远距离传递中发挥重要作用。我们发现皮肤共生菌也以与致病性金黄色葡萄球菌相似的数量和膜脂质量释放 MVs。有趣的是，皮肤共生菌的 MVs 可以通过调节人体皮肤的防御能力来防止金黄色葡萄球菌的皮肤定植。相比之下，金黄色葡萄球菌释放的 MVs 能够诱导原代人角质形成细胞中 CXCL8 和 TNF-α 的产生，招募中性粒细胞并诱导中性粒细胞胞外陷阱，从而增强金黄色葡萄球菌的皮肤定植。CXCL8 的诱导依赖于 TLR2 和 NFkB，诱导水平与 MVs 的膜脂质和蛋白 A 含量相关。有趣的是，与非病变部位的金黄色葡萄球菌菌株相比，来自 AD 患者病变皮肤的金黄色葡萄球菌菌株的 MVs 具有更高的膜脂质和蛋白 A 含量，并且具有更强的促炎潜力。我们的数据强调了宿主和细菌来源因素在金黄色葡萄球菌皮肤定植中的复杂相互作用，以及细菌来源的 MVs 及其膜脂质和蛋白 A 含量在皮肤炎症性疾病中的重要作用。
