Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2

Science. 2002 Nov 1;298(5595):1025-9. doi: 10.1126/science.1075565.

Abstract

beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology
  • Cell Line
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Drosophila Proteins*
  • Female
  • Humans
  • Interferon-alpha / physiology
  • Ligands
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Culture Test, Mixed
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Receptors, CCR6
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Chemokine / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Signal Transduction
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transfection
  • beta-Defensins / pharmacology
  • beta-Defensins / physiology*

Substances

  • Antigens, Neoplasm
  • CCR6 protein, human
  • Cancer Vaccines
  • Cytokines
  • DEFB4A protein, human
  • Drosophila Proteins
  • Interferon-alpha
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, CCR6
  • Receptors, Cell Surface
  • Receptors, Chemokine
  • Recombinant Fusion Proteins
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • beta-Defensins