Dietary deoxynucleic acid induces type 2 T-helper immune response through toll-like receptor 9 in mice

Eur J Nutr. 2011 Sep;50(6):421-6. doi: 10.1007/s00394-010-0153-4. Epub 2010 Dec 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / metabolism
  • CD4 Antigens / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • DNA / administration & dosage*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Diet*
  • Female
  • Immunomodulation*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Ovalbumin / adverse effects
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / physiology*


  • CD11c Antigen
  • CD4 Antigens
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin
  • DNA