Transcriptomic Profiling of Cutibacterium acnes IA1—Infected Keratinocytes Reveal Hub Genes and CLR Pathway in Acne Pathogenesis

Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that <i>Cutibacterium acnes</i> phylotype IA₁ contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated <i>C. acnes</i> IA1's effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live <i>C. acnes</i> IA₁ (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted <i>p</i> < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein-protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; <i>p</i> < 0.01), underscoring its role in inflammation. These findings suggest <i>C. acnes</i> IA₁ drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model's lack of in vivo skin microenvironment complexity and use of only one representative IA₁ strain.