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

Cutibacterium acnes is a common skin commensal associated with acne pathogenesis. In this study, we investigated whether acne-associated (denoted as C_A) (HL043PA1) and healthy skin-associated (denoted as C_H) (HL110PA3) C acnes strains differentially induce extracellular traps (ETs) in human neutrophils (neutrophil ETs) and T helper 17 cells (T-cell ETs [TETs]) and defined their proteomic and functional properties. Both strains triggered rapid ET release from neutrophils and T helper 17 cells. However, whereas neutrophil ETs displayed a conserved proteomic profile regardless of the 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 an 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 E coli. Gene ontology analysis revealed that neutrophil ETs 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, whereas C_A-induced TETs may promote inflammatory and tissue-remodeling responses in acne.