| Autor: |
Pohar J; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia., Lainšček D; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia., Ivičak-Kocjan K; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia., Cajnko MM; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia., Jerala R; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.; EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1000 Ljubljana, Slovenia., Benčina M; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.; EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1000 Ljubljana, Slovenia. |
| Abstrakt: |
Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9. The specific sequence motif of sODN and colocalization of ODN and sODN suggest that the mechanism of activation involves binding of both ODN and sODN to TLR9. sODNs augment TLR9 activation by mammalian genomic DNA indicating the role of short DNA degradation products in the endosomes in response to infection or in autoimmune disease, particularly at limiting concentrations of ODNs. |
