Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA (Nat Immunol, 2006, 7:49-56)

報告日期: 2006/05/09
報告時間: 17:10/18:00
報告學生: 黃聖文
講評老師: 凌 斌
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Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA

 

Gregory M Barton, Jonathan C Kagan & Ruslan Medzhitov

Nature Immunology 2006. 7(1): 49-56.

                                           

Speaker :黃聖文                                        Place: 602 room

Commentator : 凌斌                               Time: 5/9 17:10~18:00

Toll-like receptor (TLR) has a critical role in early host defense against invading pathogens. Among TLRs, TLR9 recognize unmethylated CpG-containing DNA in intracellular compartments whereas TLR4 recognize LPS on the plasma membrane. However, the biological importance of TLR subcellular localization is still not clear. In this paper, Barton et al. generated a chimeric TLR9 protein (TLR9N4C) consisting of extracellular domain of TLR9, transmembrane and the cytosolic domain of TLR4. As a result of transmembrane regions determined cellular localization, TLR9N4C was on the cell surface whereas TLR9 was in the intracellular endosome. Besides, it was found that TLR9N4C could not only recognize CpG DNA as TLR9 do, but also require neither acidification nor concentration of DNA in the endosomes. However, TLR9N4C was unable to recognize DNA delivered by herpes simplex virus 2, which suggested that endosome-lysosomal degradation of viral particles with subsequent release of nucleic acid is required for viral nucleic acid recognition via TLR9. Interestingly, TLR9N4C recognized mammalian DNA on cell surface then activated but not TLR9. Moreover, TLR9N4C activation could be abolished by DNase I, which is important in the removal of extracellular self-DNA, to prevent self-DNA from recognition of TLR9. These results demonstrated the intracellular localization of TLR9 controled access of the receptor to different sources of DNA, and it is probably critical for proper discrimination between self or foreign derived nucleic acids.