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Publication : Toll-like receptor 9 mediates CpG-DNA signaling.

First Author  Chuang TH Year  2002
Journal  J Leukoc Biol Volume  71
Issue  3 Pages  538-44
PubMed ID  11867692 Mgi Jnum  J:68228
Mgi Id  MGI:1932401 Citation  Chuang TH, et al. (2002) Toll-like receptor 9 mediates CpG-DNA signaling. J Leukoc Biol 71(3):538-44
abstractText  Among the bacterial products known to activate the innate immune '1system is bacterial DNA. This activity resides within the nonmethylated CpG motifs of the DNA and is recapitulated using appropriate synthetic CpG containing oligodeoxynucleotides (CpG-ODN). TLR9-deficient mice were shown to exhibit a nonresponsive phenotype-to-bacterial DNA and CpG-ODN. Here, we describe a model system to further characterize CpG-ODN and TLR9 interactions using ectopically expressed TLR9 in HEK293 cells. Expression of TLR9 confers cellular responsiveness to CpG-ODN but not to the other bacterial products. Previous studies identified species-specific CpG-containing sequences; here, we show that expression of murine TLR9 favors responses to CpG-ODN motifs specific to mouse cells, and expression of human TLR9 favors CpG-ODN known to preferentially activate human cells. Response patterns to various CpG-ODN motifs were parallel when cells containing an ectopically expressed TLR9 and endogenous receptor were compared. Here, we also show that TLR9 acts at the cell surface and engages an intracellular signaling pathway that includes MyD88, IRAK, and TRAF6.
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