CpG-containing immunostimulatory DNA sequences elicit TNF-α-dependent toxicity in rodents but not in humans

Journal of Clinical Investigation

Volumn 119, Issue 9, 2009, Pages 2564-2576

  Campbell, John D ^a   Cho, Yan ^a   Foster, Martyn L ^b   Kanzler, Holger ^a   Kachura, Melissa A ^a   Lum, Jeremy A ^a   Ratcliffe, Marianne J ^b   Sathe, Atul ^a   Leishman, Andrew J ^b   Bahl, Ash ^b   McHale, Mark ^b   Coffman, Robert L ^a   Hessel, Edith M ^a  

^a Dynavax Technologies Corporation   (United States)

^b ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CPG CONTAINING IMMUNOSTIMULATORY DNA SEQUENCE 1018; DNA; ETANERCEPT; IMMUNOSTIMULATING AGENT; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ALLERGY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; ASCARIS SUUM; CONTROLLED STUDY; CPG ISLAND; DNA SEQUENCE; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOSTIMULATION; IMMUNOTOXICITY; IN VITRO STUDY; LUNG ALVEOLUS MACROPHAGE; MACROPHAGE; MONKEY; MONOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; SPECIES DIFFERENCE; SPUTUM SMEAR; WEIGHT REDUCTION;

ADJUVANTS, IMMUNOLOGIC; ADMINISTRATION, INHALATION; ANIMALS; ASTHMA; BRONCHOALVEOLAR LAVAGE FLUID; CYTOKINES; DENDRITIC CELLS; HUMANS; LUNG; MACACA FASCICULARIS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; OLIGODEOXYRIBONUCLEOTIDES; SPECIES SPECIFICITY; TOLL-LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR-ALPHA;

EID: 70349202192     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI38294     Document Type: Article

References (51)

1. Hemmi, H., et al. 2000. A Toll-like receptor recognizes bacterial DNA. Nature. 408:740-745. (Pubitemid 32015992)
2. Krieg, A.M. 2006. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 5:471-484. (Pubitemid 44136959)
3. Marshall, J.D., Heeke, D.S., Abbate, C., Yee, P., and Van Nest, G. 2006. Induction of interferon-gamma from natural killer cells by immunostimulatory CpG DNA is mediated through plasmacytoid-dendritic- cell-produced interferon-alpha and tumour necrosis factor-alpha. Immunology. 117:38-46.
4. Broide, D., et al. 1998. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation and airway hyperresponsiveness in mice. J. Immunol. 161:7054-7062. (Pubitemid 28562256)
5. Sur, S., et al. 1999. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J. Immunol. 162:6284-6293. (Pubitemid 29314994)
6. Serebrisky, D., et al. 2000. CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma. J. Immunol. 165:5906-5912. (Pubitemid 30836205)
7. Jain, V.V., et al. 2002. CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma. J. Allergy Clin. Immunol. 110:867-872. (Pubitemid 36005873)
8. Kline, J.N., Kitagaki, K., Businga, T.R., Jain, V.V. 2002. Treatment of established asthma in a murine model using CpG oligodeoxynucleotides. Am. J. Physiol. Lung Cell Mol. Physiol. 283:L170-L179. (Pubitemid 34764554)
9. Hessel, E.M., et al. 2005. Immunostimulatory oligonucleotides block allergic lung inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction. J. Exp. Med. 202:1563-1573.
10. Fanucchi, M.V., et al. 2004. Immunostimulatory oligonucleotides attenuate airways remodeling in allergic monkeys. Am. J. Respir. Crit. Care Med. 170:1153-1157.
11. Tulic, M.K., et al. 2004. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J. Allergy Clin. Immunol. 113:235-241.
12. Simons, F.E.R., Shikishima, Y., Van Nest, G., Eiden, J.J., and HayGlass, K.T. 2004. Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J. Allergy Clin. Immunol. 113:1144-1151. (Pubitemid 38857998)
13. Creticos, P.S., et al. 2006. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N. Engl. J. Med. 355:1445-1455. (Pubitemid 44511559)
14. Krieg, A.M., Efler, S.M., Wittpoth, M., Al Adhami, M.J., and Davis, H.L. 2004. Induction of systemic Th1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CpG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27:460-471. (Pubitemid 39447354)
15. Gauvreau, G.M., Hessel, E.M., Boulet, L-P., Coffman, R.L., and O'Byrne, P.M. 2006. Immunostimulatory sequences regulate interferon-inducible geness but not allergic airway responses. Am. J. Respir. Crit. Care Med. 174:15-20.
16. Schwartz, D.A., et al. 1997. CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract. J. Clin. Invest. 100:68-73.
17. Knuefermann, P., et al. 2007. CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo. Respir. Res. 8:72-80.
18. Hornung, V., et al. 2002. Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168:4531-4537. (Pubitemid 34441357)
19. Bernasconi, N.L., Onai, N., and Lanzavecchia, A. 2003. A role for Toll-like receptors in acquired immunity: up-regulation of TLR-9 by BCR triggering in naïve B cells and constitutive expression in memory B cells. Blood. 101:4500-4504. (Pubitemid 36857820)
20. Rothenfusser, S., Tuma, E., Endres, S., and Hartmann, G. 2002. Plasmacytoid dendritic cells: the key to CpG. Hum. Immunol. 63:1111-1119. (Pubitemid 36025985)
21. Suzuki, K., et al. 2005. Impaired Toll-like receptor 9 expression in alveolar macrophages with no sensitivity to CpG DNA. Am. J. Respir. Crit. Care Med. 171:707-713. (Pubitemid 40471140)
22. Martin-Orozco, E., et al. 1999. Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences. Int. Immunol. 11:1111-1118. (Pubitemid 29338753)
23. Gilliet, M., et al. 2002. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/ macrophage colony-stimulating factor. J. Exp. Med. 195:953-958. (Pubitemid 34286765)
24. + T cell survival. J. Immunol. 172:6065-6073.
25. Ketloy, C., et al. 2008. Expression and function of Toll-like receptors on dendritic cells and other antigen- presenting cells from non-human primates. Vet. Immunol. Immunopathol. 125:18-30.
26. Lenz, P., Lowy, D.R., and Schiller, J.T. 2005. Papilloma virus-like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells. Eur. J. Immunol. 35:1548-1556. (Pubitemid 40691435)
27. Tracey, K.J., and Cerami, A. 1990. Metabolic responses to cachectin/TNF-α. Ann. N. Y. Acad. Sci. 587:325-331.
28. Mancuso, G., et al. 2007. Type 1 IFN signaling is crucial for host resistance against different species of pathogenic bacteria. J. Immunol. 178:3126-3133. (Pubitemid 46333194)
29. Biondo, C., et al. 2008. IFN-α/β signaling is required for polarization of cytokine responses toward a protective type 1 pattern during experimental cryptococcosis. J. Immunol. 181:566-573.
30. Nansen, A., and Thomsen, A.R. 2001. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-α/β. J. Immunol. 166:982-988. (Pubitemid 32060254)
31. Peschon, J.J., et al. 1998. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J. Immunol. 160:943-952. (Pubitemid 28049339)
32. Muller, U., et al. 1994. Functional role of type I and type II interferons in antiviral defense. Science. 264:1918-1921. (Pubitemid 24245635)
33. Schroder, K., et al. 2007. Differential effects of CpG DNA on IFN-β induction and STAT1 activation in murine macrophages versus dendritic cells: alternatively activated STAT1 negatively regulates TLR signaling in macrophages. J. Immunol. 179:3495-3503.
34. Sparwasser, T., et al. 1997. Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor alpha-mediated shock. Eur. J. Immunol. 27:1671-1679. (Pubitemid 27302848)
35. Sweet, M.J., et al. 2002. Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of Toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. J. Immunol. 168:392-399.
36. Edwards, A.D., et al. 2003. Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines. Eur. J. Immunol. 33:827-833.
37. Kadowaki, N., et al. 2001. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194:863-870. (Pubitemid 32983021)
38. Krug, A., et al. 2001. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur. J. Immunol. 31:3026-3037. (Pubitemid 32994554)
39. Demedts, I.K., Bracke, K.R., Maes, T., Joos, G.F., and Brusselle, G.C. 2006. Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. Am. J. Respir. Cell Mol. Biol. 35:387-393. (Pubitemid 44353407)
40. Bohle, B., Orel, L., Kraft, D., and Ebner, C. 2001. Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-α in human B lymphocytes: possible adjuvants for Th1 responses. J. Immunol. 166:3743-3748. (Pubitemid 32224897)
41. Teleshova, N., et al. 2006. Local and systemic effects of intranodally injected CpG-C immunostimulatory- oligodeoxyribonucleotides in macaques. J. Immunol. 177:8531-8541. (Pubitemid 44893815)
42. Abel, K., et al. 2005. Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells. Clin. Diagn. Lab. Immunol. 12:606-621. (Pubitemid 41184721)
43. Jozsef, L., Khreiss, T., Kebir, D.E., and Filep, J.G. 2006. Activation of TLR-9 induces IL-8 secretion through peroxynitrite signaling in human neutrophils. J. Immunol. 176:1195-1202. (Pubitemid 43099723)
44. Wong, C.K., Cheung, F.Y., Ip, W.K., and Lam, C.W.K. 2007. Intracellular signaling mechanisms regulating Toll-like receptor-mediated activation of eosinophils. Am. J. Respir. Cell Mol. Biol. 37:85-96.
45. Sundstrom, J.B., Little, D.M., Villinger, F., Ellis, J.E., and Ansari, A.A. 2004. Signaling through Toll-like receptors triggers HIV-1 replication in latently infected mast cells. J. Immunol. 172:4391-4401. (Pubitemid 38375254)
46. Zhu, F-G., and Marshall, J.S. 2001. CpG-containing oligodeoxynucleotides induce TNF-α and IL-6 production but not degranulation from murine bone marrow-derived mast cells. J. Leukoc. Biol. 69:253-262.
47. Matsushima, H., Yamada, N., Matsue, H., and Shimada, S. 2004. TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J. Immunol. 173:531-541. (Pubitemid 38797381)
48. Ikeda, R.K., et al. 2003. Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: modulation by immunostimulatory DNA sequences. J. Immunol. 171:4860-4867.
49. Fearon, K., et al. 2003. A minimal human immunostimulatory CpG motif that potently induces IFN-gamma and IFN-alpha production. Eur. J. Immunol. 33:2114-2122. (Pubitemid 37010028)
50. Hart, T.K., et al. 2001. Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J. Allergy Clin. Immunol. 108:250-257.
51. 2 receptors inhibits TNF-α release from human alveolar macrophages. Eur. Respir. J. 29:986-994.