Toxin-Triggered Interleukin-1 Receptor Signaling Enables Early-Life Discrimination of Pathogenic versus Commensal Skin Bacteria

Cell Host Microbe. 2019 Dec 11;26(6):795-809.e5. doi: 10.1016/j.chom.2019.10.007. Epub 2019 Nov 26.


The host must develop tolerance to commensal microbes and protective responses to infectious pathogens, yet the mechanisms enabling a privileged relationship with commensals remain largely unknown. Skin colonization by commensal Staphylococcus epidermidis facilitates immune tolerance preferentially in neonates via induction of antigen-specific regulatory T cells (Tregs). Here, we demonstrate that this tolerance is not indiscriminately extended to all bacteria encountered in this early window. Rather, neonatal colonization by Staphylococcus aureus minimally enriches for antigen-specific Tregs and does not prevent skin inflammation upon later-life exposure. S. aureus α-toxin contributes to this response by stimulating myeloid cell production of IL-1β, which limits S. aureus-specific Tregs. Loss of α-toxin or the IL-1 receptor increases Treg enrichment, whereas topical application of IL-1β or α-toxin diminishes tolerogenic responses to S. epidermidis. Thus, the preferential activation of a key alarmin pathway facilitates early discrimination of microbial "foe" from "friend," thereby preventing tolerance to a common skin pathogen.

Keywords: IL-1; commensal; dendritic cells; neonatal; pathogen; regulatory T cells; skin bacteria; skin immunity; staphylococcus.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / metabolism
  • Host Microbial Interactions / immunology
  • Immune Tolerance
  • Mice
  • Receptors, Interleukin-1 / immunology
  • Receptors, Interleukin-1 / metabolism*
  • Signal Transduction / immunology
  • Skin / microbiology*
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / immunology
  • Staphylococcus epidermidis / immunology
  • Symbiosis / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Virulence / immunology


  • Bacterial Toxins
  • Receptors, Interleukin-1