A Toll-like receptor recognizes bacterial DNA (vol 408, pg 740, 2000)

DNA from bacteria has stimulatory effects on mammalian immune cells(1-3), w hich depend on the presence of unmethylated CpG dinucleotides in the bacter ial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotide s, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like infla mmatory response(4-7). Accumulating evidence has revealed the therapeutic p otential of CpG DNA as adjuvants for vaccination strategies for cancer, all ergy and infectious diseases(8-10). Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclea r. Here we show that cellular response to CpG DNA is mediated by a Toll-lik e receptor, TLR9. TLR9-deficient (TLR9(-/-)) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9(-/-) mi ce showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-h elper type-1 response was also abolished in TLR9(-/-) mice. Thus, vertebrat e immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.