| First Author | Haas T | Year | 2008 |
| Journal | Immunity | Volume | 28 |
| Issue | 3 | Pages | 315-23 |
| PubMed ID | 18342006 | Mgi Jnum | J:133111 |
| Mgi Id | MGI:3777737 | Doi | 10.1016/j.immuni.2008.01.013 |
| Citation | Haas T, et al. (2008) The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation. Immunity 28(3):315-23 |
| abstractText | CpG motifs within phosphorothioate (PS)-modified DNA drive Toll-like receptor 9 (TLR9) activation, but the rules governing recognition of natural phosphodiester (PD) DNA are less understood. Here, we showed that the sugar backbone determined DNA recognition by TLR9. Homopolymeric, base-free PD 2' deoxyribose acted as a basal TLR9 agonist as it bound to and activated TLR9. This effect was enhanced by DNA bases, even short of CpG motifs. In contrast, PS-modified 2' deoxyribose homopolymers acted as TLR9 and TLR7 antagonists. They displayed high affinity to both TLRs and did not activate on their own, but they competitively inhibited ligand-TLR interaction and activation. Although addition of random DNA bases to the PS 2' deoxyribose backbone did not alter these effects, CpG motifs transformed TLR9-inhibitory to robust TLR9-stimulatory activity. Our results identified the PD 2' deoxyribose backbone as an important determinant of TLR9 activation by natural DNA, restrict CpG-motif dependency of TLR9 activation to synthetic PS-modified ligands, and define PS-modified 2' deoxyribose as a prime effector of TLR9 and TLR7 inhibition. |
