Vertebrates have evolved innate immune defense mechanisms that recognize and 
respond to structural patterns that are specific to microbial molecules. One 
such pattern recognition system is based on unmethylated CpG dinucleotides in 
particular sequence contexts (CpG motifs); these motifs are common in bacterial 
DNA but are under-represented ("CpG suppression") and methylated in vertebrate 
DNA. Mice that are injected with bacterial DNA or synthetic 
oligodeoxynucleotides (ODNs) containing CpG motifs respond with a rapid 
production of IL-12 and IFN-gamma. The serum levels of IL-12 were increased for 
at least 8 days after a single injection of CpG ODNs, but IFN-gamma levels 
returned to baseline within 24 h. This Th1-like cytokine response to CpG motifs 
induces a state of resistance to infection by Listeria monocytogenes in 
susceptible specific pathogen-free BALB/c mice. Resistance developed within 48 h 
of pretreatment with CpG ODNs, persisted for at least 2 wk, and was dependent 
upon IFN-gamma secretion. These data support the hypothesis that CpG DNA motifs 
are a "danger signal" that activates protective innate immune defenses and may 
have therapeutic potential.