Immune Activation and Glycolytic Responses to Cutibacterium acnes Cell Wall Polysaccharides

Carbohydrates are key components of many microbial cell walls and play a versatile role in immune recognition. Here, we analyzed the carbohydrate cell wall composition of Cutibacterium acnes strains associated with healthy skin (C H ) and acne-prone-skin (C A ) to understand their influence on host immune responses in acne. We identified glucose, mannose, and galactose as the primary monosaccharides, with minor amounts of fucose, N-acetylgalactosamine (GalNAc), and N-acetylglucosamine (GlcNAc). Linkage analysis revealed structural variations between C H and C A strains: C H strains showed a balanced and diverse polysaccharide structure, while C A strains displayed a more rigid structure with 1→4 and branched 1→6 linkages, potentially contributing to inflammatory properties. Immunostimulatory assays revealed that C. acnes carbohydrates induced IL-6 and IL-17, but not IL-1β, highlighting the role of carbohydrate structures in influencing cytokine responses. Treatment with sodium meta-periodate impaired this immunostimulatory activity, indicating that carbohydrate integrity is crucial for immune activation. Additionally, analysis of single cell RNA sequencing data from acne lesions revealed elevated glycolytic activity in acne lesions in comparison to nonlesional skin, suggesting a Warburg-like effect that promotes inflammation. Our findings highlight the role of C. acnes polysaccharides in immune modulation and inflammation, suggesting their potential as therapeutic targets for acne treatment.