Elsevier

Advances in Immunology

Volume 73, 1999, Pages 329-368
Advances in Immunology

Bacterial CpG DNA Activates Immune Cells to Signal Infectious Danger

https://doi.org/10.1016/S0065-2776(08)60790-7Get rights and content

Publisher Summary

DNA was primarily viewed as a blueprint for genetic information but essentially as immunologically inert. Compelling evidence now shows that the prokaryotic DNA—through pattern recognition—is sensed by cells of the immune system, thereby signaling “infectious danger.” Central to its physiological relevance is the question whether “sensing” of CpG DNA reflects an evolutionary vestige of the innate system to signal infectious danger. If pathogen-derived CpG DNA is sensed and evaluated via pattern recognition receptors, the brisk cell activation observed may be classified as an ancestral stress response to potentially genotoxic foreign DNA. In contrast to the codon-based nucleotide triplets used to translate amino acid sequences, immune cells sense as a “danger code” the CpG dinucleotides, in a particular base sequence context, termed “CpG motifs.” The frequency of these CpG motifs differs in eukaryotic and prokaryotic DNA—in fact, in mammalian DNA the cytosine is commonly methylated at the C-5 position. In the present scenario, there is a change in the view of interplay between the innate and the adaptive immune system. The latter is thought of as the finest accomplishment of vertebrate immunity because it creates—via somatic recombination—an abundance of antigen receptors that are able to evaluate all possible antigenic structures. To exploit the unique and potent capacity of CpG DNA for therapeutic application in humans is one of the many challenges of modern science.

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