Immune Modulation by Different Types of β2→1-Fructans Is Toll-Like Receptor Dependent

Abstract

Introductionβ2→1-fructans are dietary fibers. Main objectives of this study were 1) to demonstrate direct signalling of β2→1-fructans on immune cells, 2) to study whether this is mediated by the pattern recognition receptors Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain-containing proteins (NODs), and 3) to relate the observed effects to the chain length differences in β2→1-fructans.MethodsFour different β2→1-fructan formulations were characterised for their chain length profile. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with β2→1-fructans, and production of IL-1Ra, IL-1β, IL-6, IL-10, IL-12p70, and TNF-α was analysed. Reporter cells for TLRs and NODs were incubated with β2→1-fructans and analysed for NF-κB/AP-1 activation.ResultsCytokine production in human PBMCs was dose- and chain length-dependent. Strikingly, short chain enriched β2→1-fructans induced a regulatory cytokine balance compared to long chain enriched β2→1-fructans as measured by IL-10/IL-12 ratios. Activation of reporter cells showed that signalling was highly dependent on TLRs and their adapter, myeloid differentiation primary response protein 88 (MyD88). In human embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5, 7, 8, and NOD2 were mildly activated.Conclusionsβ2→1-fructans possess direct signalling capacity on human immune cells. By activating primarily TLR2, and to a lesser extent TLR4, 5, 7, 8, and NOD2, β2→1-fructan stimulation results in NF-κB/AP-1 activation. Chain length of β2→1-fructans is important for the induced activation pattern and IL-10/IL-12 ratios.

Cellulose alters the expression of nuclear factor kappa B-related genes and Toll-like receptor-related genes in human peripheral blood mononuclear cells

“…Activation of Toll-like receptor (TLR)2 by a specific Lactobacillus strain has demonstrated important intestinal homeostatic properties (Karczewski et al, 2010), such as regulation of human intestinal tight junction proteins and protection of the epithelial barrier, an important physical barrier belonging to the innate immune system. Previous studies in our group suggest that similar TLR-related mechanisms occur upon contact with specific dietary carbohydrates (Vogt et al, 2013(Vogt et al, , 2014, and evidence is emerging that dietary fibres can be beneficial for intestinal epithelial barrier function by activation of innate immune receptors of intestinal epithelial cells (Abreu, 2010;Cario, 2008;Hiemstra, Bouma, Geerts, Kraal, & den Haan, 2012;Karczewski et al, 2010;Vogt et al, 2014). This indicates that TLR activation is an important parameter to include in the study of cellulose-mediated immune effects.…”

“…Several dietary carbohydrates have shown the shared property of activating innate immune receptors (Brown et al, 2002;de Kivit, Kraneveld, Garssen, & Willemsen, 2011;Vogt et al, 2013), which we propose is also an important method of influencing health, by directly modulating the immune system. Activation of Toll-like receptor (TLR)2 by a specific Lactobacillus strain has demonstrated important intestinal homeostatic properties (Karczewski et al, 2010), such as regulation of human intestinal tight junction proteins and protection of the epithelial barrier, an important physical barrier belonging to the innate immune system.…”

“…In addition, the same Lactobacillus strain was found to modulate cytokine profiles in human peripheral blood mononuclear cells (PBMCs) (van Hemert et al, 2010). The cytokine balance in the intestine is important in its homeostasis, and skewing this balance with dietary carbohydrates is in our opinion, one of the relevant immunological parameters to investigate in fibre studies (Vogt et al, 2013), similar to the study of probiotic induced immune effects. As nuclear factor kappa B (NF-κB) is an essential transcription factor which is activated upon ligation of Toll-like receptors, and it plays a central role in the production of cytokines by immune cells, it was selected as an additional immunological target in this study.…”

“…Peripheral blood mononuclear cells are often applied as a model to study the immunogenic potential of dietary substances such as probiotics or prebiotics (van Hemert et al, 2010;Vogt et al, 2013), and are also known to express many TLRs (Chen et al, 2008;Siednienko & Miggin, 2009). By analysing cellulose-induced gene expression of isolated peripheral blood mononuclear cell (PBMCs) we aimed to identify genes within TLR-, and NF-κB pathways which are differentially regulated upon direct contact with cellulose.…”

Enhancement of Antioxidant Activity, Non-specific Immunity and Growth Performance of Nile Tilapia, Oreochromis Niloticus by Dietary Fructooligosaccharide

“…Moreover, acetate, propionate and lactic acid as end products of FOS fermentation play a crucial role in modulating the immune system [48]. Furthermore, FOS could interact with toll like receptors (TLR2) expressed on macrophages [49] and upregulated the expression of antimicrobial peptides (Leap) which have important role in innate immune defense and hence disease resistance of fish [12]. Parallel to this study in a previous investigations, enhanced lysozyme activity has been recorded in red drum [26], Caspian roach fry [16], turbot [13] and blunt snout bream [12,21].…”