Neutrophil extracellular trap induction defines the pathogenicity of Cutibacterium acnes clinical isolates

Summary: Abstract Body: Cutibacterium acnes is an anaerobic bacterium implicated in the pathogenesis of acne vulgaris (AV). Variations in virulence factors among C. acnes strains are thought to contribute to differences in their inflammatory potential. Neutrophil extracellular traps (NETs), antimicrobial structures released by neutrophils, play a key role in the inflammatory responses of several infectious and autoimmune diseases. This study investigates the pathogenicity of C. acnes clinical isolates by their ability to induce NETs. With Institutional Review Board approval and written informed consent, clinical isolates were collected from the facial skin of individuals with AV and healthy controls. Among 18 isolates, we identified 8 as phylotype IA1, 6 as IA2, 1 as IB, and 3 as type II. NET release and inflammatory cytokine production were significantly higher in neutrophils exposed to supernatants from certain isolates (p<0.001). NET-inducing isolates (NET-C) were more likely to exhibit β-hemolytic activity (p=0.0392) and were associated with severe disease in C. acnes-inoculated mice and AV patients. Phylogenetic analysis revealed that NET-C clustered within the camp2 gene, a co-hemolysin linked to virulence. These findings suggest that identifying NET-C isolates could enhance the evaluation and treatment of AV in clinical practice. Yi-Hsien Shih^{1, 2}, Che-Hao Hsu², Woan-Ruoh Lee^{1, 3}, Chiau-Jing Jung^{3, 4} 1. Dermatology, Taipei Medical University Shuang Ho Hospital Ministry of Health and Welfare, New Taipei, New Taipei City, Taiwan. 2. Dermatology, Taipei Medical University School of Medicine, Taipei City, Taipei City, Taiwan. 3. Taipei Medical University Graduate Institute of Medical Sciences, Taipei City, Taipei City, Taiwan. 4. Microbiology and Immunology, Taipei Medical University School of Medicine, Taipei City, Taipei City, Taiwan. Innate Immunity, Microbiology, and Microbiome