IFN-gamma primes macrophage responses to bacterial DNA

J Interferon Cytokine Res. 1998 Apr;18(4):263-71. doi: 10.1089/jir.1998.18.263.


Macrophages recognize and are activated by unmethylated CpG motifs in bacterial DNA. Here we demonstrate that production of nitric oxide (NO) from murine RAW 264 macrophages and bone marrow-derived macrophages (BMM) in response to bacterial DNA is absolutely dependent on interferon-gamma (IFN-gamma) priming. Similarly, arginine uptake and expression of the inducible nitric oxide synthase (iNOS) gene in response to bacterial DNA in BMM occurred only after IFN-gamma priming. In contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by plasmid DNA alone, and priming with IFN-gamma had no effect on this response. Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response to bacterial DNA was augmented by IFN-gamma pretreatment. In a stably transfected HIV-1 long terminal repeat (LTR) luciferase RAW 264 cell line, IFN-gamma and bacterial DNA synergized in activation of the HIV-1 LTR. Bacterial DNA has been shown to induce IFN-gamma production in vivo as an indirect consequence of interleukin-12 (IL-12) and TNF-alpha production from macrophages. The results herein suggest the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism
  • Catalase / genetics
  • Cell Line
  • DNA, Bacterial / genetics*
  • HIV-1 / genetics
  • Interferon-gamma / pharmacology*
  • Macrophages / drug effects*
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / biosynthesis
  • Repetitive Sequences, Nucleic Acid


  • DNA, Bacterial
  • RNA, Messenger
  • Nitric Oxide
  • Interferon-gamma
  • Arginine
  • Catalase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse