Department of Public Health and Applied Nutrition, Institute for Health Biosciences, The University of Tokushima, Tokushima, 770-8503, Japan.
Eur J Nutr. 2011 Sep;50(6):421-6. doi: 10.1007/s00394-010-0153-4. Epub 2010 Dec 4.
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.
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.
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.
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.
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.
研究表明，膳食核苷酸可调节免疫反应。由于核苷酸在免疫反应中具有独特的性质，因此它们在临床营养领域被用作免疫营养素。
本研究旨在探讨膳食脱氧核苷酸（DNA）对卵清蛋白（OVA）免疫的 BALB/c 小鼠抗原（Ag）特异性免疫应答的影响，并利用 Toll 样受体 9（TLR9）敲除（KO）小鼠确定其机制。
用对照和 1% DNA 饮食喂养 BALB/c 或 TLR9 KO 小鼠，并用 OVA 免疫。OVA 免疫的小鼠的脾细胞在体外用 OVA 刺激，并通过体外系统测量上清液中 IFN-γ和 IL-4 的含量。纯化 CD11c(+)树突状细胞，并检测其诱导 CD4(+)细胞产生细胞因子的能力。
DNA 组 OVA 特异性 IL-4 的产生水平明显高于对照组。相比之下，DNA 组 OVA 特异性 IFN-γ 的产生水平低于对照组。DNA 饮食降低了 TLR9 KO 小鼠的 Ag 特异性 IL-4 产生，并增强了 Ag 特异性 IFN-γ 产生。与对照组饮食喂养的小鼠相比，DNA 饮食喂养的小鼠的 CD11c(+) DC 具有更强的能力，可诱导 DO11.10 CD4(+) T 细胞产生 IL-4。
膳食 DNA 通过 TLR9 依赖途径增加 Ag 特异性 IL-4 的产生，减少 IFN-γ 的产生。CD11c(+)树突状细胞是膳食 DNA 诱导免疫调节的靶细胞。
