Human Toll-like Receptor 2 Mediates Induction of the Antimicrobial Peptide Human Beta-Defensin 2 in Response to Bacterial Lipoprotein

Eur J Immunol. 2001 Nov;31(11):3131-7. doi: 10.1002/1521-4141(200111)31:11<3131::aid-immu3131>3.0.co;2-g.

Abstract

Recognition of pathogens by Drosophila Toll or human Toll-like receptors results in translocation of Dorsal or its human homologue NF-kappaB, respectively; in Drosophila, this is followed by the production of antimicrobial peptides serving as antimicrobial effector system of the innate immune response. We investigated whether human Toll-like receptors also mediate induction of the synthesis of antimicrobial peptides. We found that HEK293 cells transfected with Toll-like receptor 2, but not wild-type cells responded to stimulation with bacterial lipoprotein by production of human beta-defensin 2. Furthermore, the human lung epithelial cell line A549 was found to constitutively express Toll-like receptor 2 and to produce beta-defensin 2 in response to bacterial lipoprotein. This response was abrogated by blocking the signaling pathway activated through Toll-like receptors by transfecting the A549 cells with a dominant-negative form of IRAK-2. Thus, exposure of human cells to bacterial lipoprotein elicits production of the antimicrobial peptide beta-defensin 2 through Toll-like receptor 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / pharmacology*
  • Cell Line
  • Drosophila Proteins*
  • Humans
  • Interleukin-1 Receptor-Associated Kinases
  • Lipoproteins / pharmacology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • NF-kappa B / metabolism
  • Protein Kinases / physiology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Transcription, Genetic
  • beta-Defensins / biosynthesis*

Substances

  • Bacterial Proteins
  • DEFB4A protein, human
  • Drosophila Proteins
  • Lipoproteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • beta-Defensins
  • Protein Kinases
  • Interleukin-1 Receptor-Associated Kinases