Abstract
Synthetic oligodeoxynucleotides containing CpG motifs have several immune effects such as cytokine production in normal mice. In this study, we demonstrated the protective effect of CpG ODN against Listeria monocytogenes in BALB/c and C57BL/6. With a single dose of 40 μg/mouse of CpG ODN 48 h before bacterial challenge, protection was achieved in both strains of mice based on survival rates compared with controls. Serum IL-12 from each mouse was measured by using enzyme-linked immunosorbent assay (ELISA), at day 0 (48 h after CpG treatment) and at days 5, 11, and 15 after bacterial challenge. It was shown that serum IL-12 was only elevated at day 0 in BALB/c mice. However, for C57BL/6 mice, IL-12 was elevated at days 0, 5, and 11. These data support the hypothesis that CpG DNA motifs activate protective innate immune defenses.
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References
Adams LG, Templeton JW (1998) Genetic resistance to bacterial diseases of animals. Rev. Sci Tech Off Int Epizoot 17:200–219
Anderson KV (2000) Toll signaling pathways in innate immune response. Curr Opin Immunol 12:13–19
Ashkar AA, Rosenthal KL (2002) Toll-like receptor 9, CpG DNA and innate immunity. Curr Mol Med 2:545–556
Bendelac A, Fearon DT (2000) Innate immunity/receptors and effectors of innate immunity. Curr Opin Immunol 12:11–12
Beutler B (2004) Innate immunity: an overview. Mol Immunol 40:845–859
Check W (2004) Innate immunity depends on Toll-like receptors. ASM News 70:317–322
Cheers C, McKenzie IF (1978) Resistance and susceptibility of mice to bacterial infection: genetics of listeriosis. Infect Immun 19:755–762
Czuprynski CJ, Faith NG, Steinberg H (2003) A/J mice are susceptible and C57BL/6 mice are resistant to Listeria monocytogenes infection by intragastric inoculation. Infect Immun 71:682–689
Elkins KL, Rhinehart-Jones TR, Stibitz S, Conover JS, Klinman DM (1999) Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. J Immunol 162:2291–229
Gervais F, Stevenson M, Skamene E (1984) Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus. J Immunol 132:2078–2083
Gilkeson GS, Conover J, Halpern M, Pisetsky DS, Feagin A, Klinman DM (1998) Effects of bacterial DNA on cytokine production by (NZB/NZW) F1 mice. J Immunol 161: 3890–3895
Gomis S, Babiuk L, Godson DL, Allan B, Thrush, T, Townsend H, Willson P, Waters E, Hecker R, Potter A (2003) Protection of chickens against Escherichia coli infections by DNA containing CpG motifs. Infect Immun 71:857–863
Greaves DR (2000) Innate immunity antigen recognition web alert. Curr Opin Immunol 12:9
Halpern MD, Kurlander RJ, Pisetsky DS (1996) Bacterial DNA induces murine interferon-γ production by stimulation of interleukin-12 and tumor necrosis factor-α. Cell Immunol 167:72–78
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hosino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745
Kaisho T, Akira S (2002) Toll-like receptors as adjuvant receptors. Biochim Biophys Acta 1589:1–3
Kline JN, Krieg AM (2001) CpG oligodeoxynucleotides. Prog Respir Res 31:229–232
Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM (1996) CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon γ. Immunology 93:2879–2883
Klinman DM, Conover J, Coban C (1999a) Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection. Infect Immun 67:5658–5663
Klinman DM, Verthelyi D, Takeshita F, Ishii KJ (1999b) Immune recognition of foreign DNA: a cure for bioterrorism? Immunity 11:123–129
Krieg AM (2002) CpG in bacterial DNA and their immune effects. Annu Rev Immunol 20:709–760
Krieg AM, Love-Homan L, Yi AK, Harty JT (1998) CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J Immunol 161:2428–2434
Krieg AM, Yi AK, Hartmann G (1999) Mechanisms and therapeutic application of immune stimulatory CpG DNA. Pharmacol Ther 84:113–120
Lizawa Y, Wagner RD, Czuprynski CJ (1993) Analysis of cytokine mRNA expression in Listeria-resistant C57BL/6 and Listeria-susceptible A/J mice during Listeria monocytogenes infection. Infect Immun 61:3739–3744
Medzhitov R (2001) CpG DNA: security code for host defense. Nat Immunol 2:15–16
Mullick A, Elias M, Picard S, Bourget L, Jovcevski O, Gauthier S, Tuite A, Harakidas P, Bihus C, Massie B, Gros P (2004) Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse strain. Infect Immun 72:5868–5876
Redford TW, Yi AK, Ward CT, Krieg AM (1998) Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides. J. Immunol 161:3930–3935
Sparwasser T, Miethke T, Lipford G, Borschert K, Hacker H, Heeg K, Wagner H (1997) Bacterial DNA causes septic shock. Nature 386:336
Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–76
Van Andel R, Hook JR RR, Franklin CL, Besch-Williford CL, Riley LK (1998) Interleukin-12 has a role in mediating resistance of murine strains to Tyzzer’s disease. Infect Immun 66:4942–4946
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This work was supported by the research fund of Urmia University, Urmia, Iran.
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Rad, M., Ahmadi, M., Farid Hosseini, R. et al. The role of interleukine-12 in protection induced by CpG ODN against Listeria monocytogenes in BALB/c and C57BL/6. Comp Clin Path 14, 197–201 (2006). https://doi.org/10.1007/s00580-005-0594-y
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DOI: https://doi.org/10.1007/s00580-005-0594-y