The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Endosomal Translocation of Vertebrate DNA Activates Dendritic Cells via TLR9-Dependent and -Independent Pathways
Open accessAbstract
TLRs discriminate foreign from self via their specificity for pathogen-derived invariant ligands, an example being TLR9 recognizing bacterial unmethylated CpG motifs. In this study we report that endosomal translocation of CpG DNA via the natural endocytotic pathway is inefficient and highly saturable, whereas endosomal translocation of DNA complexed to the cationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) is not. Interestingly, DOTAP-mediated enhanced endosomal translocation of otherwise nonstimulatory vertebrate DNA or of certain noncanonical CpG motifs triggers robust dendritic cell activation in terms of both up-regulation of CD40/CD69 and cytokine production, such as type I IFN and IL-6. We report that the stimulatory activity of phosphorothioated noncanonical CpG oligodeoxynucleotides is TLR9 dependent, whereas phosphodiester DNA, such as vertebrate DNA, in addition trigger TLR9-independent pathways. We propose that the inefficiency of the natural route for DNA internalization hinders low affinity TLR9 ligands in endosomes to reach threshold concentrations required for TLR9 activation. Endosomal compartmentalization of TLR9 may thus reflect an evolutionary strategy to avoid TLR9 activation by self-DNA.
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A Toll-like receptor recognizes bacterial DNA
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Self-citationSpecies-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
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Self-citationCpG motifs in bacterial DNA trigger direct B-cell activation
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Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
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Self-citationTLR9 signals after translocating from the ER to CpG DNA in the lysosome
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Cited by
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.-H., Homey, B., Cao, W., Wang, Y.-H., Su, B., Nestle, F. O., et al. (2007) · Nature · doi:10.1038/nature06116 · Cited by 1,910
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Gilliet, M., Cao, W., & Liu, Y.-J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2358 · Cited by 1,190
Recognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response
Stetson, D. B., & Medzhitov, R. (2006) · Immunity · doi:10.1016/j.immuni.2005.12.003 · Cited by 1,008
Beignon, A.-S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26032 · Cited by 673
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Metadata
- Authors
- Yasuda, K., Yu, P., Kirschning, C. J., Schlatter, B., Schmitz, F., Heit, A., Bauer, S., Hochrein, H., & Wagner, H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-05
- Volume
- 174
- Issue
- 10
- Pages
- 6129-6136
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2161253720
- Cited by
- 255
- References
- 44
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yasuda, K., Yu, P., Kirschning, C. J., Schlatter, B., Schmitz, F., Heit, A., Bauer, S., Hochrein, H., & Wagner, H. (2005). Endosomal Translocation of Vertebrate DNA Activates Dendritic Cells via TLR9-Dependent and -Independent Pathways. The Journal of Immunology. https://doi.org/10.4049/jimmunol.174.10.6129
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