Cheung Caroline T, Lancien Ugo, Corvec Stéphane, Mengeaud Valérie, Mias Céline, Véziers Joëlle, Khammari Amir, Dréno Brigitte
Nantes University, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy (INCIT), Nantes, France.
Nantes University, CHU Nantes Chirurgie Plastique, Reconstructrice et Esthétique et Centre de traitement des Brûlés, Hôtel-Dieu, Nantes, France.
Exp Dermatol. 2024 Aug;33(8):e15150. doi: 10.1111/exd.15150.
Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA, IA, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne-like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA from an inflammatory acne lesion was different from C. acnes phylotype IA from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human β-defensin 2 (hBD2), cathelicidin (LL-37), interleukin (IL)-1β, IL-6, IL-8, IL-17α and IL-36γ, and ELISA for IL-6, IL-8 and IL-17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro-inflammatory cytokines and anti-microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne-associated inflammation in vitro and that C. acnes phylotype IA collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro.
痤疮是一种慢性炎症性皮肤病，与痤疮丙酸杆菌（C. acnes）有关，该菌可分为六个主要系统发育型（IA、IA、IB、IC、II和III）。痤疮的发展与痤疮丙酸杆菌系统发育型多样性的丧失有关，其特征是IA型系统发育型相对于其他系统发育型过度生长。研究还表明，痤疮丙酸杆菌分泌的纯化细胞外囊泡（EVs）可在皮肤模型中诱导类似痤疮的炎症反应。我们旨在确定来自炎症性痤疮病变的痤疮丙酸杆菌IA型系统发育型分泌的EVs的炎症特征是否与来自正常皮肤的痤疮丙酸杆菌IA型系统发育型不同，从而在炎症严重程度中发挥直接作用。在体外培养痤疮丙酸杆菌IA型系统发育型的两个临床菌株后产生EVs，这两个菌株分别是来自正常人皮肤的T5和来自炎症性痤疮病变的A47，然后将其与人永生化角质形成细胞、HaCaT细胞或从腹部整形术中获得的皮肤外植体一起孵育。随后，对人β-防御素2（hBD2）、cathelicidin（LL-37）、白细胞介素（IL）-1β、IL-6、IL-8、IL-17α和IL-36γ进行定量PCR（qPCR），并对IL-6、IL-8和IL-17α进行ELISA检测。我们发现，与来自正常人皮肤的EVs相比，来自炎症性痤疮病变的痤疮丙酸杆菌在体外产生的EVs在转录和蛋白质水平上均显著增加了促炎细胞因子和抗菌肽。我们首次表明，来自炎症性痤疮的痤疮丙酸杆菌EVs在体外痤疮相关炎症中起关键作用，并且从炎症性痤疮病变和正常皮肤中收集的痤疮丙酸杆菌IA型系统发育型在体外产生不同的EVs和炎症特征。
