Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12

Clin Immunol Immunopathol. 1997 Aug;84(2):185-93. doi: 10.1006/clin.1997.4380.


Bacterial DNA (bDNA) activates B cells and macrophages and can augment inflammatory responses by inducing release of proinflammatory cytokines. We found that bDNA stimulation of mouse spleen cells induced NK cell IFN-gamma production that was dependent upon the presence of unmethylated CpG motifs, and oligonucleotides with internal CpG motifs could also induce splenocytes to secrete IFN-gamma. The bDNA-induced IFN-gamma response was strictly macrophages dependent. While splenocytes from SCID mice secreted IFN-gamma in response to bDNA, depletion of macrophages eliminated this response. Additionally, purified NK cells did not respond to bDNA; however, addition of macrophages restored the NK cell IFN-gamma response. Coculture of NK cells with preactivated macrophages further increased bDNA-induced NK cell IFN-gamma production. Anti-IL-12 or IL-10 inhibited bDNA-induced IFN-gamma response. Treatment of purified macrophages with bDNA resulted in IL-12 secretion accompanied by an increase in IL-12 p40 mRNA level. Although isolated NK cells did not make IFN-gamma in response to bDNA, NK cells costimulated with IL-12 gained the ability to respond to bDNA. These experiments show that bDNA induces macrophage IL-12 production which, in turn, stimulates NK cell IFN-gamma production. Macrophage-derived IL-12 renders NK cells responsive to bDNA permitting an even greater IFN-gamma response to bDNA.

Publication types

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

MeSH terms

  • Animals
  • DNA, Bacterial / pharmacology*
  • Female
  • Interferon-gamma / biosynthesis*
  • Interleukin-10 / pharmacology
  • Interleukin-12 / metabolism*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Macrophage Activation / immunology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology


  • DNA, Bacterial
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma