Phenotype and antimicrobial activity of Th17 cells induced by Propionibacterium acnes strains associated with healthy and acne skin

摘要

Studies of human skin microbiome suggest that Propionibacterium acnes strains may contribute differently to skin health and disease. However, the immune phenotype and functions of Th17 cells induced by healthy (PH) vs. acne (PA) skin-associated P. acnes strains are currently unknown. We stimulated PBMCs from healthy donors and observed that PA strains induce higher IL-17 levels than PH strains. We next generated PH and PA strain-specific Th17 clones and show that P. acnes strains induce Th17 cells of varied phenotype and function that are stable in the presence of IL-2 and IL-23. Although PH and PA-specific clones expressed similar levels of LL-37 and DEFB4, only PH-specific clones secreted molecules sufficient to kill P. acnes. Furthermore, electron microscopic studies revealed that supernatants derived from activated PH and not PA-specific clones exhibited robust bactericidal activity against P. acnes, and complete breaches in the bacterial cell envelope were observed. This antimicrobial activity was independent of IL-26, as both natural IL-26 released by Th17 clones and rhIL-26 lacked antimicrobial potency against P. acnes. Overall, our data suggest that P. acnes strains may differentially modulate the CD4⁺ T cell responses, leading to the generation of Th17 cells that may contribute to either homeostasis or acne pathogenesis.