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. In this study, we analyzed the carbohydrate cell wall composition of Cutibacterium acnes strains associated with healthy skin (denoted as C_H) and acne-prone skin (denoted as 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, and N-acetylglucosamine. Linkage analysis revealed structural variations between C_H and C_A strains: C_H strains showed a balanced and diverse polysaccharide structure, whereas 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. In addition, analysis of single-cell RNA-sequencing data from acne lesions revealed elevated glycolytic activity in acne lesions in comparison with that in 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.