Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-alpha-mediated shock

Eur J Immunol. 1997 Jul;27(7):1671-9. doi: 10.1002/eji.1830270712.


Cell surface components of pathogens, such as lipopolysaccharide (LPS), are an important signal for receptor-mediated activation of immune cells. Here we demonstrate that DNA of gram-positive and gram-negative bacteria or certain synthetic oligonucleotides displaying unmethylated CpG-motifs can trigger macrophages in vitro to induce nuclear translocation of nuclear factor-kappa B, accumulate tumor necrosis factor (TNF)-alpha mRNA and release large amounts of TNF-alpha. In vivo these events culminate in acute cytokine-release syndrome which includes systemic but transient accumulation of TNF-alpha. D-Galactosamine (DGalN)-sensitized mice succumb to lethal toxic shock due to macrophage-derived TNF-alpha resulting in fulminant apoptosis of liver cells. LPS and a specific oligonucleotide synergized in vivo as measured by TNF-alpha-release, suggesting that macrophages integrate the respective signals. The ability of macrophages to discriminate and to respond to bacterial DNA with acute release of pro-inflammatory cytokines may point out an important and as yet unappreciated sensing mechanism for foreign DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Base Composition / immunology
  • DNA, Bacterial / administration & dosage
  • DNA, Bacterial / immunology*
  • DNA, Bacterial / pharmacology
  • Drug Synergism
  • Galactosamine / immunology
  • Injections, Intraperitoneal
  • Lipopolysaccharides / administration & dosage
  • Liver / immunology
  • Liver / metabolism
  • Macrophage Activation / drug effects
  • Macrophage Activation / genetics
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / microbiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, SCID
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / pharmacology
  • Shock, Septic / genetics
  • Shock, Septic / immunology*
  • Shock, Septic / microbiology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / physiology*


  • DNA, Bacterial
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Tumor Necrosis Factor-alpha
  • Galactosamine