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

Correction

关键词: CELL WALL COMPONENTS;    DENDRITIC CELLS;    CUTTING EDGE;    CPG-DNA;    DROSOPHILA TOLL;    ACTIVATION;    MATURATION;    MOTIFS;    MICE;    TLR4;   

DOI  :  10.1038/35054604

来源: SCIE

【 摘 要 】

DNA from bacteria has stimulatory effects on mammalian immune cells(1-3), which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response(4-7). Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases(8-10). Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like 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(-/-) mice 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-helper type-1 response was also abolished in TLR9(-/-) mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.

【 授权许可】

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