Potential functionality of Cutibacterium acnes extracellular vesicles in atopic dermatitis and acne vulgaris: A comparative proteomic analysis

BACKGROUND: Cutibacterium acnes is a commensal bacterium residing in healthy skin and plays a critical role in maintaining skin homeostasis. C. acnes has been considered closely related to acne vulgaris, while recent studies suggest that C. acnes and its metabolites may have a protective role in atopic dermatitis (AD) by modulating the immune system and maintaining skin homeostasis. Extracellular vesicles (EVs) are small membranous vesicles secreted by bacteria that participate in bacteria-host interactions. METHODS: This study first compared C. acnes EVs from AD lesions (AD-EVs), acne lesions (Acne-EVs), and healthy skin (NC-EVs), using Label-free quantitative LC-MS/MS and validated differently expressed proteins by parallel reaction monitoring (PRM). Then Normal Human Epidermal Keratinocytes (NHEK) and human primary keratinocytes (KC) were treated with C. acnes EVs isolated from different groups, and the expressions of inflammatory factors were measured by quantitative real-time PCR and Western blotting. RESULTS: Compared with the acne group, the AD group showed greater downregulation of proteins related to energy metabolism and carbon source utilization pathway. Differences in protein profile in AD and acne lesion-separated C. acnes EVs correspond to the abnormal sebum secretion pattern in both diseases. C. acnes EVs from different groups affected different expressions of Th1 and Th2 inflammatory factors and epidermal barrier markers in NHEK and KC, indicating different immunomodulatory potentials. CONCLUSIONS: This study observed distinct proteomic differences between AD-EVs and Acne-EVs, and provided insights into the functional differences of C. acnes EVs in AD and acne.