AIMES-Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
PLoS Pathog. 2024 Aug 29;20(8):e1012056. doi: 10.1371/journal.ppat.1012056. eCollection 2024 Aug.
The Staphylococcus sp. are a dominant part of the human skin microbiome and present across the body. Staphylococcus epidermidis is a ubiquitous skin commensal, while S. aureus is thought to colonize at least 30% of the population. S. aureus are not only colonizers but a leading cause of skin and soft tissue infections and a critical healthcare concern. To understand how healthy human skin may differentiate commensal bacteria, such as S. epidermidis, from the potential pathogen methicillin-resistant S. aureus (MRSA), we use ex vivo human skin models that allow us to study this host-bacterial interaction in the most clinically relevant environment. Our work highlights the role of the outer stratum corneum as a protective physical barrier against invasion by colonizing Staphylococci. We show how the structural cells of the skin can internalize and respond to different Staphylococci with increasing sensitivity. In intact human skin, a discriminatory IL-1β response was identified, while disruption of the protective stratum corneum triggered an increased and more diverse immune response. We identified and localized tissue resident Langerhans cells (LCs) as a potential source of IL-1β and go on to show a dose-dependent response of MUTZ-LCs to S. aureus but not S. epidermidis. This suggests an important role of LCs in sensing and discriminating between bacteria in healthy human skin, particularly in intact skin and provides a detailed snapshot of how human skin differentiates between friend and potential foe. With the rise in antibiotic resistance, understanding the innate immune response of healthy skin may help us find ways to enhance or manipulate these natural defenses to prevent invasive infection.
葡萄球菌属是人类皮肤微生物组的主要组成部分，存在于全身。表皮葡萄球菌是一种无处不在的皮肤共生菌，而金黄色葡萄球菌被认为至少定植于 30%的人群。金黄色葡萄球菌不仅是定植菌，还是皮肤和软组织感染的主要原因，也是严重的医疗保健关注问题。为了了解健康的人类皮肤如何将表皮葡萄球菌等共生菌与潜在的病原体耐甲氧西林金黄色葡萄球菌（MRSA）区分开来，我们使用了离体人体皮肤模型，使我们能够在最具临床相关性的环境中研究这种宿主-细菌相互作用。我们的工作强调了外层角质层作为抵御定植性葡萄球菌入侵的物理保护屏障的作用。我们展示了皮肤的结构细胞如何通过内化和对不同的葡萄球菌产生敏感性来响应。在完整的人体皮肤中，确定了具有区分能力的 IL-1β 反应，而破坏保护性角质层则引发了更广泛和更多样化的免疫反应。我们确定并定位了组织驻留的朗格汉斯细胞（LCs）作为 IL-1β 的潜在来源，并继续表明 MUTZ-LCs 对金黄色葡萄球菌而非表皮葡萄球菌具有剂量依赖性反应。这表明 LCs 在健康人体皮肤中对细菌的感应和区分中具有重要作用，尤其是在完整的皮肤中，并提供了关于人体皮肤如何区分朋友和潜在敌人的详细快照。随着抗生素耐药性的增加，了解健康皮肤的固有免疫反应可能有助于我们找到增强或操纵这些天然防御的方法，以预防侵袭性感染。
