Propionibacterium acnes-Derived Extracellular Vesicles Promote Acne-Like Phenotypes in Human Epidermis

J Invest Dermatol. 2018 Jun;138(6):1371-1379. doi: 10.1016/j.jid.2018.01.007. Epub 2018 Jan 31.

Abstract

Acne vulgaris is an inflammatory disease occurring in the pilosebaceous unit and is the most common skin condition in young people. A gram-positive bacterium, Propionibacterium acnes, has been suspected to contribute to the development of acne. Here, we report that P. acnes constitutively releases extracellular vesicles (EVs) exhibiting typical EV morphology and size. Moreover, the P. acnes-derived EVs (PEVs) can induce acne-like phenotypes in human epidermal keratinocytes and a reconstituted human skin model. PEVs significantly induced inflammatory cytokines IL-8 and GM-CSF and dysregulated epidermal differentiation by increasing proliferating keratinocytes and decreasing epidermal keratin 10 and desmocollin 1 levels. PEVs showed strong effects, evoking these responses at earlier time points compared with P. acnes extract at the same protein concentration. We verified that PEVs were internalized via clathrin-dependent endocytosis into keratinocytes and that PEV-induced cellular responses occurred via Toll-like receptor 2-dependent signal cascades. Furthermore, PEVs showed a stronger effect than keratinocytes in inducing inflammatory cytokines in myeloid cells. Collectively, our study suggests that PEVs induce acne-like phenotypes in a unique way; therefore, inhibiting the release of EVs from P. acnes or targeting PEV-mediated signaling pathways could represent an alternative method for alleviating acne occurrence and phenotypes.

MeSH terms

  • Acne Vulgaris / immunology*
  • Acne Vulgaris / microbiology
  • Acne Vulgaris / pathology
  • Cell Line
  • Epidermal Cells
  • Epidermis / immunology
  • Epidermis / metabolism
  • Extracellular Vesicles / immunology*
  • Extracellular Vesicles / metabolism
  • Gram-Positive Bacterial Infections / immunology*
  • Gram-Positive Bacterial Infections / microbiology
  • Gram-Positive Bacterial Infections / pathology
  • Humans
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Myeloid Cells / immunology
  • Primary Cell Culture
  • Propionibacterium acnes / cytology
  • Propionibacterium acnes / immunology*
  • Propionibacterium acnes / metabolism
  • RNA, Small Interfering / metabolism
  • Signal Transduction / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism

Substances

  • RNA, Small Interfering
  • TLR2 protein, human
  • Toll-Like Receptor 2