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In Vitro Evidence for Immune-Modulatory Properties of Non-Digestible Oligosaccharides: Direct Effect on Human Monocyte Derived Dendritic Cells.

Lehmann S, Hiller J, van Bergenhenegouwen J, Knippels LM, Garssen J, Traidl-Hoffmann C - PLoS ONE (2015)

Bottom Line: Oligosaccharides did not induce relevant amounts of IL-12p70 production, but did promote IL-10 release by MoDC.Furthermore, scGOS/lcFOS mixtures exerted a significant enhancing effect on LAB induced IL-10 secretion by MoDC while no increase in IL-12p70 production was observed.Our results indicate anti-inflammatory and direct, microbiota independent, immune-modulatory properties of scGOS/lcFOS mixtures on human MoDC suggesting a possible induction of regulatory T cells (Tregs).

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Augsburg, Germany; Center of Allergy and Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technische Universität & Helmholtz Zentrum München, Munich, Germany.

ABSTRACT
Infant formulas containing non-digestible oligosaccharides (NDO) similar to the composition in breast milk or a combination of lactic acid bacteria (LAB) and NDO have been shown to harbor preventive effects towards immune-regulatory disorders. The aim of this study was to investigate the immune-modulatory potential of non-digestible short chain galacto- and long chain fructo-oligosaccharides (scGOS/lcFOS) mimicking the natural distribution of oligosaccharides in human breast milk in presence or absence of certain LAB strains in human monocyte derived dendritic cells (MoDC). Immature human MoDC prepared from peripheral blood of healthy non-atopic volunteers were screened in vitro after stimulation with specific scGOS/lcFOS in presence or absence of LAB. IL-10 and IL-12p70 release was analyzed after 24 hours in cell-free supernatants by enzyme-linked immunosorbent assay (ELISA). A luminex-based assay was conducted to assess further cytokine and chemokine release by MoDC. To investigate the resulting T cell response, stimulated MoDC were co-incubated with naïve T cells in allogeneic stimulation assays and intracellular Foxp3 expression, as well as immune-suppressive capacity was determined. Oligosaccharides did not induce relevant amounts of IL-12p70 production, but did promote IL-10 release by MoDC. Furthermore, scGOS/lcFOS mixtures exerted a significant enhancing effect on LAB induced IL-10 secretion by MoDC while no increase in IL-12p70 production was observed. Blocking toll like receptor (TLR)4 abrogated the increase in IL-10 in both the direct stimulation and the LAB stimulation of MoDC, suggesting that scGOS/lcFOS act via TLR4. Finally, scGOS/lcFOS-treated MoDC were shown to upregulate the number of functional suppressive Foxp3 positive T cells following allogeneic stimulation. Our results indicate anti-inflammatory and direct, microbiota independent, immune-modulatory properties of scGOS/lcFOS mixtures on human MoDC suggesting a possible induction of regulatory T cells (Tregs). The tested combinations of LAB and scGOS/lcFOS might represent a useful dietary ingredient for the maintenance of intestinal homeostasis via the induction of Tregs.

No MeSH data available.


Related in: MedlinePlus

scGOS/lcFOS-stimulated MoDC release cytokines and chemokines in a different manner compared to LPS.MoDC were stimulated with scGOS/lcFOS (5 mg/ml) for 24h. MoDC matured by LPS served as positive control for functional stimulation. The amount of cytokines and chemokines in cell-free supernatants was measured by luminex-based assay (readout: IL-1α, IL-1β, IL-6, IL-23p19, IL-27, TNFα, IP-10, MDC (CCL22), TARC (CCL17), MIP3α (CCL20) and ELISA (IL-10, IL-12p70)). Results are presented in pg/ml. Three independent experiments are shown.
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pone.0132304.g003: scGOS/lcFOS-stimulated MoDC release cytokines and chemokines in a different manner compared to LPS.MoDC were stimulated with scGOS/lcFOS (5 mg/ml) for 24h. MoDC matured by LPS served as positive control for functional stimulation. The amount of cytokines and chemokines in cell-free supernatants was measured by luminex-based assay (readout: IL-1α, IL-1β, IL-6, IL-23p19, IL-27, TNFα, IP-10, MDC (CCL22), TARC (CCL17), MIP3α (CCL20) and ELISA (IL-10, IL-12p70)). Results are presented in pg/ml. Three independent experiments are shown.

Mentions: The observation that, in contrast to LPS, scGOS/lcFOS stimulated MoDC released IL-10 in the absence of IL-12 led us to consider whether other soluble mediators were also differentially affected. Upon comparing the LPS- with the scGOS/lcFOS-induced MoDC profile of mediator release several differences could be observed depending on the secreted mediator (Fig 3).


In Vitro Evidence for Immune-Modulatory Properties of Non-Digestible Oligosaccharides: Direct Effect on Human Monocyte Derived Dendritic Cells.

Lehmann S, Hiller J, van Bergenhenegouwen J, Knippels LM, Garssen J, Traidl-Hoffmann C - PLoS ONE (2015)

scGOS/lcFOS-stimulated MoDC release cytokines and chemokines in a different manner compared to LPS.MoDC were stimulated with scGOS/lcFOS (5 mg/ml) for 24h. MoDC matured by LPS served as positive control for functional stimulation. The amount of cytokines and chemokines in cell-free supernatants was measured by luminex-based assay (readout: IL-1α, IL-1β, IL-6, IL-23p19, IL-27, TNFα, IP-10, MDC (CCL22), TARC (CCL17), MIP3α (CCL20) and ELISA (IL-10, IL-12p70)). Results are presented in pg/ml. Three independent experiments are shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493044&req=5

pone.0132304.g003: scGOS/lcFOS-stimulated MoDC release cytokines and chemokines in a different manner compared to LPS.MoDC were stimulated with scGOS/lcFOS (5 mg/ml) for 24h. MoDC matured by LPS served as positive control for functional stimulation. The amount of cytokines and chemokines in cell-free supernatants was measured by luminex-based assay (readout: IL-1α, IL-1β, IL-6, IL-23p19, IL-27, TNFα, IP-10, MDC (CCL22), TARC (CCL17), MIP3α (CCL20) and ELISA (IL-10, IL-12p70)). Results are presented in pg/ml. Three independent experiments are shown.
Mentions: The observation that, in contrast to LPS, scGOS/lcFOS stimulated MoDC released IL-10 in the absence of IL-12 led us to consider whether other soluble mediators were also differentially affected. Upon comparing the LPS- with the scGOS/lcFOS-induced MoDC profile of mediator release several differences could be observed depending on the secreted mediator (Fig 3).

Bottom Line: Oligosaccharides did not induce relevant amounts of IL-12p70 production, but did promote IL-10 release by MoDC.Furthermore, scGOS/lcFOS mixtures exerted a significant enhancing effect on LAB induced IL-10 secretion by MoDC while no increase in IL-12p70 production was observed.Our results indicate anti-inflammatory and direct, microbiota independent, immune-modulatory properties of scGOS/lcFOS mixtures on human MoDC suggesting a possible induction of regulatory T cells (Tregs).

View Article: PubMed Central - PubMed

Affiliation: Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Augsburg, Germany; Center of Allergy and Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technische Universität & Helmholtz Zentrum München, Munich, Germany.

ABSTRACT
Infant formulas containing non-digestible oligosaccharides (NDO) similar to the composition in breast milk or a combination of lactic acid bacteria (LAB) and NDO have been shown to harbor preventive effects towards immune-regulatory disorders. The aim of this study was to investigate the immune-modulatory potential of non-digestible short chain galacto- and long chain fructo-oligosaccharides (scGOS/lcFOS) mimicking the natural distribution of oligosaccharides in human breast milk in presence or absence of certain LAB strains in human monocyte derived dendritic cells (MoDC). Immature human MoDC prepared from peripheral blood of healthy non-atopic volunteers were screened in vitro after stimulation with specific scGOS/lcFOS in presence or absence of LAB. IL-10 and IL-12p70 release was analyzed after 24 hours in cell-free supernatants by enzyme-linked immunosorbent assay (ELISA). A luminex-based assay was conducted to assess further cytokine and chemokine release by MoDC. To investigate the resulting T cell response, stimulated MoDC were co-incubated with naïve T cells in allogeneic stimulation assays and intracellular Foxp3 expression, as well as immune-suppressive capacity was determined. Oligosaccharides did not induce relevant amounts of IL-12p70 production, but did promote IL-10 release by MoDC. Furthermore, scGOS/lcFOS mixtures exerted a significant enhancing effect on LAB induced IL-10 secretion by MoDC while no increase in IL-12p70 production was observed. Blocking toll like receptor (TLR)4 abrogated the increase in IL-10 in both the direct stimulation and the LAB stimulation of MoDC, suggesting that scGOS/lcFOS act via TLR4. Finally, scGOS/lcFOS-treated MoDC were shown to upregulate the number of functional suppressive Foxp3 positive T cells following allogeneic stimulation. Our results indicate anti-inflammatory and direct, microbiota independent, immune-modulatory properties of scGOS/lcFOS mixtures on human MoDC suggesting a possible induction of regulatory T cells (Tregs). The tested combinations of LAB and scGOS/lcFOS might represent a useful dietary ingredient for the maintenance of intestinal homeostasis via the induction of Tregs.

No MeSH data available.


Related in: MedlinePlus