Cutaneous innate immune sensing of Toll-like receptor 2-6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells

Immunity. 2014 Nov 20;41(5):762-75. doi: 10.1016/j.immuni.2014.10.009. Epub 2014 Nov 13.

Abstract

Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Antigens / immunology
  • CD11b Antigen / biosynthesis
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / microbiology
  • Humans
  • Interleukin-6 / biosynthesis
  • Lipopeptides / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Cells / immunology*
  • Myeloid Differentiation Factor 88 / biosynthesis
  • Skin / immunology*
  • Skin / microbiology
  • Staphylococcal Skin Infections / immunology*
  • Staphylococcus aureus / immunology
  • Toll-Like Receptor 1 / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 6 / immunology

Substances

  • Antigens
  • CD11b Antigen
  • Interleukin-6
  • Lipopeptides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Tlr6 protein, mouse
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 6