Bacteria induce skin regeneration via IL-1β signaling

Cell Host Microbe. 2021 May 12;29(5):777-791.e6. doi: 10.1016/j.chom.2021.03.003. Epub 2021 Apr 1.

Abstract

Environmental factors that enhance regeneration are largely unknown. The immune system and microbiome are attributed roles in repairing and regenerating structure but their precise interplay is unclear. Here, we assessed the function of skin bacteria in wound healing and wound-induced hair follicle neogenesis (WIHN), a rare adult organogenesis model. WIHN levels and stem cell markers correlate with bacterial counts, being lowest in germ-free (GF), intermediate in conventional specific pathogen-free (SPF), and highest in wild-type mice, even those infected with pathogenic Staphylococcus aureus. Reducing skin microbiota via cage changes or topical antibiotics decreased WIHN. Inflammatory cytokine IL-1β and keratinocyte-dependent IL-1R-MyD88 signaling are necessary and sufficient for bacteria to promote regeneration. Finally, in a small trial, a topical broad-spectrum antibiotic also slowed skin wound healing in adult volunteers. These results demonstrate a role for IL-1β to control morphogenesis and support the need to reconsider routine applications of topical prophylactic antibiotics.

Keywords: bacteria; hair; regeneration.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Female
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Keratinocytes / metabolism
  • Keratinocytes / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbiota
  • Middle Aged
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Regeneration
  • Signal Transduction
  • Skin / metabolism
  • Skin / microbiology*
  • Skin / physiopathology*
  • Wound Healing
  • Wounds and Injuries / genetics
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / microbiology*
  • Wounds and Injuries / physiopathology*
  • Young Adult

Substances

  • Interleukin-1beta
  • Myeloid Differentiation Factor 88
  • Receptors, Interleukin-1