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CpG motif-independent activation of TLR9 upon endosomal translocation of "natural" phosphodiester DNA.
- Source :
-
European journal of immunology [Eur J Immunol] 2006 Feb; Vol. 36 (2), pp. 431-6. - Publication Year :
- 2006
-
Abstract
- Endosomally translocated host (self) DNA activates Toll-like receptor 9 (TLR9), while extracellular self-DNA does not. This inconsistency reflects poor endosomal DNA translocation but also implies that host DNA contains DNA sequences that function as ligands for TLR9. Herein we report that contrary to phosphorothioate (PS)-stabilized oligonucleotides (ODN), "natural" phosphodiester (PD) ODN lacking CpG motifs activate TLR9. CpG motif-independent TLR9 activation of Flt3-L-induced dendritic cells (DC) was dependent on enforced endosomal translocation and triggered upregulation of CD40 and CD69 as well as production of IL-6 and IFN-alpha. Binding studies utilizing surface plasmon resonance technology (Biacore) revealed low TLR9 binding to single-stranded (ss) PD-ODN lacking CpG motifs. At higher concentrations their TLR9 binding activity compared well with TLR9 binding of canonical ss PD CpG-ODN. These results imply that both the chemical modification of the DNA backbone as well as the amount of endosomally translocated DNA represent determining factors that allow CpG motif-independent activation of TLR9 by ss PD-DNA.
- Subjects :
- Animals
Biological Transport drug effects
Biological Transport immunology
Cells, Cultured
DNA, Single-Stranded metabolism
DNA, Single-Stranded pharmacology
Dendritic Cells cytology
Dendritic Cells metabolism
Endosomes metabolism
Mice
Oligodeoxyribonucleotides metabolism
Oligodeoxyribonucleotides pharmacology
Protein Binding drug effects
Protein Binding immunology
Surface Plasmon Resonance methods
Toll-Like Receptor 9 metabolism
CpG Islands immunology
DNA, Single-Stranded immunology
Dendritic Cells immunology
Endosomes immunology
Oligodeoxyribonucleotides immunology
Toll-Like Receptor 9 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 36
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16421948
- Full Text :
- https://doi.org/10.1002/eji.200535210