Cutibacterium acnes induces T-cell extracellular traps with distinct proteome programs

Cutibacterium acnes ( C. acnes) is a common skin commensal associated in acne pathogenesis. Here, we investigated whether acne-associated (HL043PA1, C A ) and healthy skin-associated (HL110PA3, C H ) C. acnes strains differentially induce extracellular traps (ET) in human neutrophils (NETs) and Th17 cells (TETs) and defined their proteomic and functional properties. Both strains triggered rapid ET release from neutrophils and Th17 cells. However, whereas NETs displayed a conserved proteomic profile regardless of strain, TETs exhibited strain-specific specialization. C A -induced TETs were enriched in inflammatory and extracellular matrix remodeling proteins, whereas C H -induced TETs showed increased abundance of nuclear, mitochondrial, and antimicrobial proteins, including granulysin, granzyme B, and cathepsin C. Functional assays demonstrated that these compositional differences translate into distinct effector programs, with C H -induced TETs mediating DNA-dependent antimicrobial activity against both C. acnes and Escherichia coli . Gene ontology analysis revealed that NETs and TETs share a core proteome, consistent with a conserved structural framework, whereas TETs exhibit greater functional specialization. Together, these findings reveal strain- and cell type-specific regulation of ET composition and function, suggesting that C H -induced TETs may contribute to skin immune homeostasis, while C A -induced TETs may promote inflammatory and tissue remodeling responses in acne.