DNase II-dependent DNA digestion is required for DNA sensing by TLR9

Nature Communications

Volumn 6, Issue , 2015, Pages

  Chan, Mei Po ^a   Onji, Masahiro ^b   Fukui, Ryutaro ^a   Kawane, Kohki ^c   Shibata, Takuma ^a,d   Saitoh, Shin Ichiroh ^a   Ohto, Umeharu ^a   Shimizu, Toshiyuki ^a,d   Barber, Glen N ^e   Miyake, Kensuke ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b OKAYAMA UNIVERSITY   (Japan)

^c KYOTO SANGYO UNIVERSITY   (Japan)

^d JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^e UNIVERSITY OF MIAMI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL DNA; CPG A LIGAND; CPG B LIGAND; DEOXYRIBONUCLEASE II; DNA FRAGMENT; GENOMIC DNA; INTERLEUKIN 12P40; LIGAND; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 2; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG; DEOXYRIBONUCLEASE; DNA;

CELL ORGANELLE; DIGESTIBILITY; ENZYME ACTIVITY; LIGAND; NERVOUS SYSTEM; PROTEIN; SENSORY SYSTEM;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL ACTIVATION; CONTROLLED STUDY; DENDRITIC CELL; DNA DEGRADATION; ENZYME ACTIVITY; LYSOSOME; MALE; MOUSE; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; ANIMAL; METABOLISM;

BACTERIA (MICROORGANISMS);

ANIMALS; DENDRITIC CELLS; DNA; ENDODEOXYRIBONUCLEASES; LYSOSOMES; MALE; MICE; TOLL-LIKE RECEPTOR 9;

EID: 84936781864     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms6853     Document Type: Article

References (27)

1. Atianand, M. K. & Fitzgerald, K. A. Molecular basis of DNA recognition in the immune system. J. Immunol. 190, 1911-1918 (2013).
2. Krieg, A. CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol. 20, 709-760 (2002).
3. Krug, A. et al. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur. J. Immunol. 31, 2154-2163 (2001).
4. Vollmer, J. et al. Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur. J. Immunol. 34, 251-262 (2004).
5. Kerkmann, M. et al. Spontaneous formation of nucleic acid-based nanoparticles is responsible for high interferon-α induction by CpG-A in plasmacytoid dendritic cells. J. Biol. Chem. 280, 8086-8093 (2005).
6. Barton, G. M. & Kagan, J. C. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat. Rev. Immunol. 9, 535-542 (2009).
7. Barrat, F. J. et al. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202, 1131-1139 (2005).
8. Lande, R. et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564-569 (2007).
9. Ganguly, D. et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 206, 1983-1994 (2009).
10. Yasutomo, K. et al. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat. Genet. 28, 313-314 (2001).
11. Napirei, M. et al. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat. Genet. 25, 177-181 (2000).
12. Kawane, K. et al. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 443, 998-1002 (2006).
13. Gall, A. et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 36, 120-131 (2012).
14. Barber, G. N. Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Curr. Opin. Immunol. 23, 10-20 (2011).
15. Ahn, J., Gutman, D., Saijo, S. & Barber, G. N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl Acad. Sci. USA 109, 19386-19391 (2012).
16. Okabe, Y., Kawane, K., Akira, S., Taniguchi, T. & Nagata, S. Toll-like receptorindependent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. J. Exp. Med. 202, 1333-1339 (2005).
17. Gautier, G. et al. A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells. J. Exp. Med. 201, 1435-1446 (2005).
18. Cheng, Y. C., Hsueh, C. C., Lu, S. C. & Liao, T. H. Identification of three crucial histidine residues (His115, His132 and His297) in porcine deoxyribonuclease II. Biochem. J. 398, 177-185 (2006).
19. Onji, M. et al. An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing. Nat. Commun. 4, 1949 (2013).
20. Honda, K. et al. Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434, 1035-1040 (2005).
21. Guiducci, C. et al. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J. Exp. Med. 203, 1999-2008 (2006).
22. Sasai, M., Linehan, M. M. & Iwasaki, A. Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 329, 1530-1534 (2010).
23. Ohkouchi, S. et al. Biogenesis and proteolytic processing of lysosomal DNase II. PLoS One 8, e59148 (2013).
24. Huang, L. et al. Cutting edge: DNA sensing via the STING adaptor in myeloid dendritic cells induces potent tolerogenic responses. J. Immunol. 191, 3509-3513 (2013).
25. Fearon, K. et al. A minimal human immunostimulatory CpG motif that potently induces IFN-gamma and IFN-alpha production. Eur. J. Immunol. 33, 2114-2122 (2003).
26. Hartmann, G. et al. Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. Eur. J. Immunol. 33, 1633-1641 (2003).
27. Rigby, R. E. et al. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J. 33, 542-558 (2014).