Activation of toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10

J Immunol. 2000 Oct 1;165(7):3804-10. doi: 10.4049/jimmunol.165.7.3804.

Abstract

Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP and LPS results in a TLR-dependent induction of immunomodulatory genes leading to the production of pro-inflammatory cytokines. In this paper, we compared the expression and response of TLRs on monocytes and dendritic cells (DC). TLR2, but not TLR4, was detected on peripheral blood monocytes and DC, in lymphoid tissue CD1alpha+ DC as well as on in vitro monocyte-derived DC. Upon stimulation with bLP or LPS, monocytes produced IL-12 and IL-10 at similar levels, whereas monocyte-derived DC produced comparable levels of IL-12, but little IL-10. Greater than 90% of the bLP-induced production of IL-12 was blocked by anti-TLR2 mAb. Thus, DC express TLR2 and activation of this receptor by bLP provides an innate mechanism by which microbial pathogens preferentially activate cell-mediated immunity.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Bacterial Proteins / chemical synthesis
  • Bacterial Proteins / pharmacology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Drosophila Proteins*
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / biosynthesis*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / physiology
  • Lipoproteins / chemical synthesis
  • Lipoproteins / pharmacology
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / blood
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cell Surface / physiology
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Bacterial Proteins
  • Drosophila Proteins
  • Interleukin-6
  • Lipoproteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12