Mechanisms of TLR9 activation
Open Access
- 1 December 2004
- journal article
- other
- Published by SAGE Publications in Innate Immunity
- Vol. 10 (6), 406-412
- https://doi.org/10.1177/09680519040100060501
Abstract
Non-methylated CpG-motifs in bacterial or viral DNA are recognized by TLR9 as foreign. The activation of TLR9 by microbial DNA or synthetic oligonucleotides based on these motifs leads to the induction of innate immune responses. We have compared the subcellular localization of fluorescent versions of TLR9 and TLR4 and found that TLR9 is expressed in the endoplasmic reticulum while TLR4 is expressed on the plasma membrane. Fluorescently tagged bacterial DNA or CpG-DNA was observed to traffic to a tubular lysosomal compartment in human pDCs. In stimulated cells, TLR9 translocated to CpG-DNA or microbial DNA containing structures in the endosome, where TLR9 binds to DNA and initiates signaling.Keywords
This publication has 45 references indexed in Scilit:
- Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8Science, 2004
- Rational design of new CpG oligonucleotides that combine B cell activation with high IFN‐α induction in plasmacytoid dendritic cellsEuropean Journal of Immunology, 2003
- Toll-Like ReceptorsAnnual Review of Immunology, 2003
- CpG Motifs in Bacterial DNA and Their Immune EffectsAnnual Review of Immunology, 2002
- The Role of DNA Methylation in Mammalian EpigeneticsScience, 2001
- Identification of CpG oligonucleotide sequences with high induction of IFN-α/β in plasmacytoid dendritic cellsEuropean Journal of Immunology, 2001
- A Toll-like receptor recognizes bacterial DNANature, 2000
- An innate sense of dangerSeminars in Immunology, 1998
- CpG motifs in bacterial DNA trigger direct B-cell activationNature, 1995
- The immune system evolved to discriminate infectious nonself from noninfectious selfImmunology Today, 1992