Staphylococcus epidermidis Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense

J Innate Immun. 2019;11(2):125-135. doi: 10.1159/000492162. Epub 2018 Sep 3.


Bacterial challenge of keratinocytes with the abundant skin commensal Staphylococcus epidermidis induces distinct innate immune responses, but the underlying molecular mechanisms are still emerging. We report that the aryl hydrocarbon receptor (AhR) was activated in human primary keratinocytes infected with S. epidermidis, leading to induction of the AhR-responsive gene cytochrome P450 1A1 (CYP1A1). In addition, functional AhR was required for S. epidermidis-mediated induction of IL-1β expression in keratinocytes. AhR-dependent gene induction of IL-1β and CYP1A1 was mediated by factor(s) < 2 kDa secreted by S. epidermidis. Blockade of the AhR in a 3D organotypic skin equivalent infected with S. epidermidis attenuated the S. epidermidis-induced CYP1A1 and IL-1β expression. Moreover, S. epidermidis also induced expression of IL-1α and of the antimicrobial peptide human β-defensin-3 in an AhR-dependent manner in a 3D skin equivalent. An increased outgrowth of S. epidermidis on the surface of skin explants treated with a specific AhR inhibitor further indicate a pivotal role of the AhR in mediating an epidermal defense response. Taken together, our data expand the role of the AhR in innate immunity and support a previously unappreciated contribution for the AhR in cutaneous defense.

Keywords: Aryl hydrocarbon receptor; Cutaneous innate defense; IL-1β; Staphylococcus epidermidis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytochrome P-450 CYP1A1 / genetics
  • Humans
  • Immunity, Innate
  • Interleukin-1beta / genetics
  • Keratinocytes / physiology*
  • Organ Culture Techniques
  • RNA, Small Interfering / genetics
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction
  • Skin / immunology*
  • Skin / pathology
  • Skin Diseases / metabolism*
  • Staphylococcal Infections / metabolism*
  • Staphylococcus epidermidis / physiology*
  • Transcriptional Activation


  • Interleukin-1beta
  • RNA, Small Interfering
  • Receptors, Aryl Hydrocarbon
  • Cytochrome P-450 CYP1A1