Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88

The innate immune system evolved to recognize conserved microbial products, termed pathogen-associated molecular patterns (PAMPs), which are invariant among diverse groups of microorganisms. PAMPs are recognized by a set of g erm-line encoded pattern recognition receptors (PRRs), Among the best chara cterized PAMPs are bacterial lipopolysaccharide (LPS), peptidoglycan (PGN), mannans, and other constituents of bacterial and fungal cell walls, as wel l as bacterial DNA. Recognition of bacterial DNA is the most enigmatic of t hese, as it depends on a particular sequence motif, called the CpG motif, i n which an unmethylated CpG present in a particular sequence context accoun ts for a potent immunostimulatory activity of CpG DNA. Receptor(s) of the i nnate immune system that mediate recognition of CpG DNA are currently unkno wn. Here, we report that recognition of CpG DNA requires MyD88, an adaptor protein involved in signal transduction by the Toll-like receptors (TLRs), essential components of innate immune recognition in both Drosophila and ma mmals [1,2]. Signaling induced by CpG DNA was found to be unaffected in cel ls deficient in TLR2 or TLR4, suggesting that some other member of the Toll family mediates recognition of bacterial DNA.