The Anti-Inflammatory Activities of Propionibacterium acnes CAMP Factor-Targeted Acne Vaccines

J Invest Dermatol. 2018 Nov;138(11):2355-2364. doi: 10.1016/j.jid.2018.05.032. Epub 2018 Jun 30.

Abstract

Inflammatory acne vulgaris afflicts hundreds of millions of people globally. Propionibacterium acnes, an opportunistic skin bacterium, has been linked to the pathogenesis of acne vulgaris. Our results show that a secretory Christie-Atkins-Munch-Petersen (CAMP) factor of P. acnes is up-regulated in anaerobic cultures. Mutation of CAMP factor significantly diminishes P. acnes colonization and inflammation in mice, demonstrating the essential role of CAMP factor in the cytotoxicity of P. acnes. Vaccination of mice with CAMP factor considerably reduced the growth of P. acnes and production of MIP-2, a murine counterpart of human IL-8. Acne lesions were collected from patients to establish an ex vivo acne model for validation of the efficacy of CAMP factor antibodies in the neutralization of the acne inflammatory response. The P. acnes CAMP factor and two proinflammatory cytokines (IL-8 and IL-1β) were expressed at higher levels in acne lesions than those in nonlesional skin. Incubation of ex vivo acne explants with monoclonal antibodies to CAMP factor markedly attenuated the amounts of IL-8 and IL-1β. Our work using an ex vivo acne model shows that P. acnes CAMP factor is an essential source of inflammation in acne vulgaris.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / genetics
  • Acne Vulgaris / immunology*
  • Animals
  • Antibodies, Blocking / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Vaccines / immunology*
  • Cells, Cultured
  • Chemokine CXCL2 / metabolism
  • Female
  • Gram-Positive Bacterial Infections / immunology*
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / immunology*
  • Humans
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mutation
  • Propionibacterium acnes / pathogenicity
  • Propionibacterium acnes / physiology*
  • Skin / microbiology
  • Skin / pathology*
  • Vaccination
  • Virulence
  • Virulence Factors / genetics
  • Virulence Factors / immunology*

Substances

  • Antibodies, Blocking
  • Bacterial Proteins
  • Bacterial Vaccines
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Hemolysin Proteins
  • Interleukin-18
  • Interleukin-1beta
  • Virulence Factors