IFN-gamma primes macrophage responses to bacterial DNA

M J Sweet, K J Stacey, D K Kakuda, D Markovich, D A Hume

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)263-71
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 1998

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Arginine
  • Catalase
  • Cell Line
  • DNA, Bacterial
  • HIV-1
  • Interferon-gamma
  • Macrophages
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • RNA, Messenger
  • Repetitive Sequences, Nucleic Acid

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