Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs and activate immune cells that express the TLR9 receptor. This triggers the production of reactive oxygen species and the secretion of proinflammatory cytokines and chemokines. Under some conditions these effects can result in the systemic inflammatory response syndrome. Under other conditions, the immune stimulatory effects of CpG motifs can protect against pathogen challenge and initiate prophylactic and therapeutic innate and adaptive immune responses.