The actions of bacterial DNA on murine macrophages

D P Sester, K J Stacey, M J Sweet, S J Beasley, S L Cronau, D A Hume

Research output: Contribution to journalArticlepeer-review

Abstract

Murine macrophages are able to distinguish bacterial from mammalian DNA. The response is mimicked by single-stranded oligonucleotides containing unmethylated CG dinucleotides ("CpG" motifs) in specific sequence contexts. The dose-response curve for activation is influenced by variation in the sequence flanking the core CpG motif. CpG or bacterial DNA activates several signaling pathways in common with bacterial lipopolysaccharide (LPS), leading to induction of cytokine genes such as tumor necrosis factor alpha. Pretreatment with LPS causes desensitization to subsequent activation by CpG DNA. Both stimuli also cause cell cycle arrest in macrophages proliferating in response to the macrophage growth factor colony-stimulating factor-1 (CSF-1), but prevent apoptosis caused by growth factor removal. In part, cell cycle arrest by CpG DNA and LPS may be linked to rapid down-modulation of the CSF-1 receptor from the cell surface, a response that occurs in an all-or-nothing manner. The response of macrophages to CpG DNA has aspects in common with the DNA damage response in other cell types, which may provide clues to the underlying mechanism.
Original languageEnglish
Pages (from-to)542-8
Number of pages7
JournalJournal of Leukocyte Biology
Volume66
Issue number4
Publication statusPublished - Oct 1999

Keywords

  • Animals
  • Cell Differentiation
  • CpG Islands
  • Cytokines
  • DNA, Bacterial
  • Down-Regulation
  • Humans
  • Lipopolysaccharides
  • Macrophage Activation
  • Macrophages
  • Mice
  • Receptor, Macrophage Colony-Stimulating Factor
  • Th1 Cells

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