Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2 immune responses in a murine model - PubMed (original) (raw)
Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2 immune responses in a murine model
N Takahashi et al. Clin Exp Immunol. 2006 Jul.
Abstract
We have reported previously that novel immunostimulatory sequence (ISS) oligodeoxynucleotide (ODN) BL07S from a probiotic strain of Bifidobacterium longum inhibited immunoglobulin (Ig) E production in vitro. However, whether ISS-ODNs from probiotics regulate T helper type 2 (Th2)-polarized immune reactions in vivo remains unclear. To evaluate the inhibitory effects of ODN BL07S on type I allergic response, BALB/c mice were injected with or without ODN BL07S in the presence of ovalbumin (OVA) on days 0 and 14. Serum Ig levels (IgE, IgG1 and IgG2a) and cytokine levels (interferon (IFN)-gamma, interleukin (IL)-12, IL-4, IL-5, IL-10 and IL-13) were investigated in splenocyte cultures from days 14-28. Production of OVA-specific and total IgE were significantly suppressed by administration of ODN BL07S, but not by ODN BL06S, a non-ISS-ODN. Compared to controls, ODN BL07S induced significantly lower levels of Th2 cytokines (IL-4 and IL-5) in splenocyte cultures, and significantly higher levels of serum OVA-specific IgG2a. These effects of ODN BL07S on modulation of Th2 immune response were dose-dependent. The present results demonstrate that ODN BL07S from genomic DNA of B. longum BB536 prevents antigen-induced Th2 immune responses in vivo, suggesting that ISS-ODNs from probiotics might be useful in preventing allergic disease.
Figures
Fig. 1
Oligodeoxynucleotide (ODN) BL07S decreased IgE production in immunized mice. Mice were immunized using ovalbumin (OVA) (20 µg/mouse) and ODN BL07S (10 µg/mouse) in alum at a 2-week interval. As controls, mice were administered OVA and phosphate buffered saline (PBS) in alum. Blood was collected on day 21 and IgE levels were determined using enzyme-linked immunosorbent assay. Data represent mean ± s.d. from six mice per group. (a) OVA-specific IgE; (b) total IgE. *P < 0·05, **P < 0·01 versus controls.
Fig. 2
Effects of oligodeoxynucleotide (ODN) BL07S on total and ovalbumin (OVA)-specific Ig levels in serum of mice sensitized with OVA. Mice were immunized as described in Fig. 1. Ig levels were determined using enzyme-linked immunosorbent assay. Data represent mean ± s. d. from eight mice per group. (•) Control group; (○) ODN BL07S group. (a) OVA-specific IgE; (b) total IgE; (c) OVA-specific IgG2a; (d) total IgG2a; (e) OVA-specific IgG1; (f) total IgG1. *P < 0·05, **P < 0·01 versus controls. †Below the limits of detection.
Fig. 3
Cytokine levels in supernatants of cultured splenocytes from mice sensitized with ovalbumin (OVA). Mice were immunized as described in Fig. 1. Spleens were removed on days 14, 21 or 28 and single splenocytes were incubated with 100 µg/ml OVA for 72 h. Cytokine levels were determined using enzyme-linked immunosorbent assay. Data represent mean ± s. d. from eight mice per group. (•) Control group; (○) oligodeoxynucleotide (ODN) BL07S group; (▴) naive group. (a) Interleukin (IL)-12; (b) interferon (IFN)-γ; (c) IL-4; (d) IL-5; (e) IL-13. *P < 0·05, **P < 0·01 versus controls. †Below the limits of detection.
Fig. 4
Dose–response of oligodeoxynucleotide (ODN) BL07S on Ig levels in serum of mice. Mice were immunized with ovalbumin (OVA) (20 µg/mouse) and ODN BL07S (0·1 µg, 1 µg and 10 µg/mouse) in alum at a 2-week interval. Sera were collected on day 21. Ig levels in sera were determined using enzyme-linked immunosorbent assay. Results represent mean ± s.d. of serum from eight mice per group. (a) OVA-specific IgE; (b) total IgE; (c) OVA-specific IgG2a; (d) total IgG2a; (e) OVA-specific IgG1; (f) total IgG1. *P < 0·05, **P < 0·01 versus controls.
Fig. 5
Effects of oligodeoxynucleotide (ODN) BL07S dose on cytokine production of mice. Mice were immunized as described in Fig. 4. Spleens were removed on day 21 and single splenocytes were incubated with 100 µg/ml ovalbumin (OVA) for 72 h. Cytokine levels of supernatants were determined using enzyme-linked immunosorbent assay. Data represent mean ± s.d. from eight mice per group. (a) Interleukin (IL)-12; (b) interferon (IFN)-γ; (c) IL-4; (d) IL-5; (e) IL-13. *P < 0·05, **P < 0·01 versus controls. †Below the limits of detection.
Fig. 6
Interleukin (IL)-10 and transforming growth factor (TGF)-β levels in supernatants of cultured splenocytes. Mice were immunized with ovalbumin (OVA) (20 µg/mouse) and oligodeoxynucleotide (ODN) BL07S (1 µg or 10 µg/mouse) in alum at 2-week intervals. Spleens were removed on day 21 and single splenocytes were incubated with or without 100 µg/ml OVA. Cytokine levels of supernatants were determined using enzyme-linked immunosorbent assay. Levels of IL-10 in supernatants without OVA were below the limit of detection. Data represent mean ± s.d. of serum from six mice per group. **P < 0·01 versus controls. †Below the limits of detection.
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