Abstract
Background
It has been shown that dietary nucleotides modulate immune response. Due to their unique properties in immune responses, nucleotides are used as immunonutrition in the field of clinical nutrition.
Aim of the study
In this study, we examined the effect of dietary deoxynucleic acid (DNA) on antigen (Ag)-specific immune response in ovalbumin (OVA)-immunized BALB/c mice and determined the mechanism using toll-like receptor 9 (TLR9) knock-out (KO) mice.
Methods
BALB/c or TLR9 KO mice were fed control and 1% DNA diets and immunized with OVA. Spleen cells from OVA-immunized mice were stimulated with OVA in vitro, and the contents of IFN-γ and IL-4 in supernatants were measured by an ex vivo system. CD11c+ dendritic cells were purified, and ability of cytokine induction to CD4+ cells was examined.
Results
The level of OVA-specific IL-4 production in the DNA group was significantly higher than that in the control group. In contrast, the level of OVA-specific IFN-γ production in the DNA group was lower than that in the control group. The DNA diet decreased Ag-specific IL-4 production and enhanced Ag-specific IFN-γ production in TLR9 KO mice. CD11c+ DCs from mice fed the DNA diet had a greater ability than CD11c+ DCs from mice fed the control diet to induce the production of IL-4 from DO11.10 CD4+ T cells.
Conclusions
Dietary DNA increases Ag-specific IL-4 production and decreases IFN-γ production through a TLR9-dependent pathway. CD11c+ dendritic cells are target cells in dietary DNA-induced immune regulation.
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References
Aggett P, Leach JL, Rueda R, MacLean WC Jr (2003) Innovation in infant formula development: a reassessment of ribonucleotides in 2002. Nutrition 19:375–384
Pickering LK, Granoff DM, Erickson JR, Masor ML, Cordle CT, Schaller JP, Winship TR, Paule CL, Hilty MD (1998) Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 101:242–249
Schaller JP, Kuchan MJ, Thomas DL, Cordle CT, Winship TR, Buck RH, Baggs GE, Wheeler JG (2004) Effect of dietary ribonucleotides on infant immune status. Part 1: humoral responses. Pediatr Res 56:883–890
Buck RH, Thomas DL, Winship TR, Cordle CT, Kuchan MJ, Baggs GE, Schaller JP, Wheeler JG (2004) Effect of dietary ribonucleotides on infant immune status. Part 2: immune cell development. Pediatr Res 56:891–900
Bower RH, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, Van Buren CT, Rothkopf MM, Daly JM, Adelsberg BR (1995) Early enteral administration of a formula (impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med 23:436–449
Braga M, Gianotti L, Vignali A, Di Carlo V (1998) Immunonutrition in gastric cancer surgical patients. Nutrition 14:864–865
Kubo C, Johnson BC, Gajjar A, Good RA (1987) Crucial dietary factors in maximizing life span and longevity in autoimmune-prone mice. J Nutr 117:1129–1135
Carver JD (1994) Dietary nucleotides: cellular immune, intestinal and hepatic system effect. J Nutr 124:S144–S148
Yamauchi K, Adjei AA, Ameho CK, Chan YC, Kulkarni AD, Sato S, Okamoto K, Yamamoto S (1996) A nucleoside-nucleotide mixture and its components increase lymphoproliferative and delayed hypersensitivity responses in mice. J Nutr 126:1571–1577
Jyonouchi H, Sun S (1996) An orally supplemented mononucleotide mixture prevents the decrease in T cell-dependent humoral immunity in C57BL/6 mice fed a nucleotide-free diet. J Nutr 126:1586–1593
Jyonouchi H, Sun S, Sato S (1996) Nucleotide-free diet suppresses antigen-driven cytokine production by primed T cells: effects of supplemental nucleotides and dietary fatty acids. Nutrition 12:608–615
Jyonouchi H, Sun S, Abiru T, Winship T, Kuchan MJ (2000) Dietary nucleotides modulate antigen-specific type 1 and type 2 T-cell responses in young C57BL/6 mice. Nutrition 16:442–446
Nagafuchi S, Hachimura S, Totsuka M, Takahashi T, Goto M, Yajima T, Kuwata T, Habu S, Kaminogawa S (2000) Dietary nucleotides can up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice. Int Arch Allergy Immunol 122:33–341
Sudo Naiba Y, Takaki A, Tanaka K, Yu XN, Oyama N, Koga Y, Kubo C (2000) Dietary nucleic acids promote a shift in Th1/Th2 balance toward Th1-dominant immunity. Clin Exp Allergy 30:979–987
Jyonouchi H, Sun S, Winship T, Kuchan MJ (2001) Dietary ribonucleotides modulate type 1 and type 2 T-helper cell responses against ovalbumin in young BALB/cJ mice. J Nutr 131:1165–1170
Jyonouchi H, Sun S, Winship T, Kuchan MJ (2003) Dietary ribonucleotides increase antigen-specific type 1 T-helper cells in the regional draining lymph nodes in young BALB/cJ mice. Nutrition 19:41–46
Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T (2003) Integration of interferon alpha/beta signaling to p53 responses in tumor suppression and antiviral defense. Nature 424:516–523
Kogiso M, Sakai T, Mitsuya K, Komatsu T, Yamamoto S (2006) Genistein suppresses antigen-specific immune responses through competition with 17β-estradiol for estrogen receptors in ovalbumin-immunized BALB/c mice. Nutrition 22:802–809
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357
Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173
Wagner H (1999) Bacterial CpG DNA activates immune cells to signal infectious danger. Adv Immunol 73:329–368
Vollmer J, Weeratna RD, Jurk M, Samulowitz U, McCluskie MJ, Payette P, Davis HL, Schetter C, Krieg AM (2004) Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology 113:212–223
McCluskie MJ, Weeratna RD, Davis HL (2001) The potential of oligodeoxynucleotides as mucosal and parenteral adjuvants. Vaccine 19:2657–2660
McCluskie MJ, Davis HL (2000) Oral, intrarectal and intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants. Vaccine 19:413–422
Sano K, Shirota H, Terui T, Hattori T, Tamura G (2003) Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner. J Immunol 170:2367–2373
Fedianina LN, Zaitseva EA, Epshtein LM, Besednova NN, Somov GP (2005) Experimental study on impact of salmon milt DNA on T-cellular immunity. Antibiot Khimioter 50:14–17
Besednova NN, Kasianenko I, Epshtein LM, Gazha AK (1999) The immunotropic properties of the deoxyribonucleic acid from Salmonidase milt. Antibiot Khimioter 44:13–15
Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921–929
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939
Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:940–945
Acknowledgments
This work was partly supported by Grant-in-Aid for Scientific Research. We thank Drs. Nemoto H. and Kataoka K. for technical analyses.
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The authors of this research disclose any potential conflict of interest.
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Nakamoto, M., Shuto, E., Hosaka, T. et al. Dietary deoxynucleic acid induces type 2 T-helper immune response through toll-like receptor 9 in mice. Eur J Nutr 50, 421–426 (2011). https://doi.org/10.1007/s00394-010-0153-4
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DOI: https://doi.org/10.1007/s00394-010-0153-4