The sweetness of the DNA backbone drives Toll-like receptor 9 Export

@article{citeulike:3112215, abstract = {The prevailing paradigm ascribes activation of Toll-like receptor 9 (TLR9) to the detection of CpG-motifs within pathogen derived DNA. However, new work ties natural phospho-diester (PD) DNA recognition by TLR9 to the detection of the DNA sugar backbone 2' deoxyribose. PD 2' deoxyribose homopolymers lacking DNA bases (abasic) are shown to act as TLR9 agonist while abasic phospho-thioate (PS) 2' deoxyribose functions as TLR9 antagonist. Alignment of bases to PD 2' deoxyribose enhanced its TLR9 agonistic function, while only CpG-motifs introduced to inhibitory PS 2' deoxyribose converted the antagonistic activity into powerful agonistic function. These new data thus restrict the CpG-motif dependency of TLR9 activation to the promising group of immunopharmacons that are based on PS modified synthetic DNA. They also show that natural PD DNA drives TLR9 activation sequence-independently as is the case for ds RNA recognizing TLR3 and ss RNA recognizing TLR7 and TLR8. Thus evolutionary pressure might have exiled nucleic acid recognizing TLRs such as TLR9 to endosomes in order to avoid activation by host (self) derived nucleic acids.}, author = {Wagner, Hermann}, booktitle = {Host-Pathogen Interactions / Antibody Therapeutics - Edited by Tsuneyasu Kaisho and Hermann Wagner / Edited by Paul Parren and Jan van de Winkel}, citeulike-article-id = {3112215}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.coi.2008.06.013}, citeulike-linkout-1 = {http://www.sciencedirect.com/science/article/B6VS1-4T3KP8Y-1/2/27066a673b341817e02dd147bb729219}, doi = {10.1016/j.coi.2008.06.013}, journal = {Current Opinion in Immunology}, keywords = {dna, review, tlr9}, month = {August}, number = {4}, pages = {396--400}, posted-at = {2008-08-12 17:18:28}, priority = {3}, title = {The sweetness of the DNA backbone drives Toll-like receptor 9}, url = {http://dx.doi.org/10.1016/j.coi.2008.06.013}, volume = {20}, year = {2008} }

TY - JOUR ID - citeulike:3112215 L3 - citeulike-article-id:3112215 N2 - The prevailing paradigm ascribes activation of Toll-like receptor 9 (TLR9) to the detection of CpG-motifs within pathogen derived DNA. However, new work ties natural phospho-diester (PD) DNA recognition by TLR9 to the detection of the DNA sugar backbone 2' deoxyribose. PD 2' deoxyribose homopolymers lacking DNA bases (abasic) are shown to act as TLR9 agonist while abasic phospho-thioate (PS) 2' deoxyribose functions as TLR9 antagonist. Alignment of bases to PD 2' deoxyribose enhanced its TLR9 agonistic function, while only CpG-motifs introduced to inhibitory PS 2' deoxyribose converted the antagonistic activity into powerful agonistic function. These new data thus restrict the CpG-motif dependency of TLR9 activation to the promising group of immunopharmacons that are based on PS modified synthetic DNA. They also show that natural PD DNA drives TLR9 activation sequence-independently as is the case for ds RNA recognizing TLR3 and ss RNA recognizing TLR7 and TLR8. Thus evolutionary pressure might have exiled nucleic acid recognizing TLRs such as TLR9 to endosomes in order to avoid activation by host (self) derived nucleic acids. IS - 4 JF - Current Opinion in Immunology EP - 400 TI - The sweetness of the DNA backbone drives Toll-like receptor 9 VL - 20 T2 - Host-Pathogen Interactions / Antibody Therapeutics - Edited by Tsuneyasu Kaisho and Hermann Wagner / Edited by Paul Parren and Jan van de Winkel SP - 396 KW - dna KW - review KW - tlr9 AU - Wagner, Hermann PY - 2008/08// UR - http://dx.doi.org/10.1016/j.coi.2008.06.013 ER -