Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through toll-like receptor 2

Microbes Infect. 2006 May;8(6):1513-21. doi: 10.1016/j.micinf.2006.01.008. Epub 2006 Apr 7.

Abstract

The epidermis, which covers the surface of all mammals, serves as a front line of defense against the invasion of pathogenic microbes and acts as a crucial site for innate immune responses. Various antimicrobial molecules are expressed not only on the surfaces of monocytes but also on epithelial cells. beta-Defensins, a family of antimicrobial peptides, are produced by several types of epithelial cells, including keratinocytes. However, the induction pathways for beta-defensins in keratinocytes are not fully understood. We hypothesized that bacterial components would trigger the expression of beta-defensins in keratinocytes through a toll-like receptor (TLR)-MyD88 signaling pathway that plays important roles in innate immunity. Production of TNF-alpha and IL-1 alpha following stimulation with lipopolysaccharide or bacterial lipopeptides was completely abolished in TLR2&TLR4-doubly deficient keratinocytes and in MyD88-deficient keratinocytes. Expression of murine beta-defensin was upregulated by bacterial lipopeptides in wild-type keratinocytes, while it was attenuated in TLR2-deficient keratinocytes. To evaluate the in vivo role of TLRs in keratinocytes, we inoculated Staphylococcus aureus into the tail skin from TLR2-deficient mice that had been grafted on the dorsal skin of syngeneic mice. The grafted skin from TLR2-deficient mice resulted in erosion. These studies strongly suggest that the TLR2-MyD88-dependent pathway in keratinocytes is essential for antimicrobial activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biopsy
  • Blotting, Western
  • Epidermis / drug effects
  • Epidermis / immunology
  • Epidermis / metabolism
  • Epidermis / microbiology
  • Immunohistochemistry
  • Interleukin-1 / biosynthesis
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Lipoproteins / metabolism
  • Lipoproteins / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Diseases, Bacterial / immunology
  • Skin Diseases, Bacterial / metabolism
  • Skin Diseases, Bacterial / microbiology
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • beta-Defensins / biosynthesis*
  • beta-Defensins / deficiency
  • beta-Defensins / genetics
  • beta-Defensins / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • DEFB103A protein, human
  • Interleukin-1
  • Lipopolysaccharides
  • Lipoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • beta-Defensins