β-(1→4)-Mannobiose Acts as an Immunostimulatory Molecule in Murine Dendritic Cells by Binding the TLR4/MD-2 Complex.

Ting-Yu Cheng,Masako Toda,Stefan Schülke,Stefan Vieths,Wataru Saburi,Stephan Scheurer,Yen-Ju Lin

doi:10.3390/cells10071774

Ting-Yu Cheng, Masako Toda + Show 5 more

Open Access

https://doi.org/10.3390/cells10071774

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Journal: Cells	Publication Date: Jul 14, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Tohoku University, Paul Ehrlich Institut, Hokkaido University

Abstract

Some β-mannans, including those in coffee bean and soy, contain a mannose backbone with β-(1→4) bonds. Such mannooligosaccharides could have immunological functions involving direct interaction with immune cells, in addition to acting as prebiotics. This study aimed at assessing the immunological function of mannooligosaccharides with β-(1→4) bond, and elucidating their mechanism of action using bone marrow-derived murine dendritic cells (BMDCs). When BMDCs were stimulated with the mannooligosaccharides, only β-Man-(1→4)-Man significantly induced production of cytokines that included IL-6, IL-10, TNF-α, and IFN-β, and enhanced CD4+ T-cell stimulatory capacity. Use of putative receptor inhibitors revealed the binding of β-Man-(1→4)-Man to TLR4/MD2 complex and involvement with the complement C3a receptor (C3aR) for BMDC activation. Interestingly, β-Man-(1→4)-Man prolonged the production of pro-inflammatory cytokines (IL-6 and TNF-α), but not of the IL-10 anti-inflammatory cytokine during extended culture of BMDCs, associated with high glucose consumption. The results suggest that β-Man-(1→4)-Man is an immunostimulatory molecule, and that the promotion of glycolysis could be involved in the production of pro-inflammatory cytokine in β-Man-(1→4)-Man-stimulated BMDCs. This study could contribute to development of immune-boosting functional foods and a novel vaccine adjuvant.

Highlights

Mannans are D-mannose-based polysaccharides that comprise the outermost layer of the cell wall in plants, fungi, and yeast [1]
This reduction of IL-2 production is likely due to overstimulation of CD4+ T-cells. It is consistent with our previous study showing, that overstimulation of OT-II cells with modified OVA reduced T-cell activation in co-culture with bone marrow-derived murine dendritic cells (BMDCs) [17]. These results suggest, that Man2 can enhance the CD4+ T-cell stimulatory capacity of BMDCs
The concentration of the IL-10 anti-inflammatory cytokine in the cell culture supernatant of Man2-stimulated cells was significantly lower than that in LPS-stimulated cells (Figure 7C). These results suggest that Man2 prolongs the secretion of pro-inflammatory cytokines, associated with increased glucose metabolism

Summary

Introduction

Mannans are D-mannose-based polysaccharides that comprise the outermost layer of the cell wall in plants, fungi, and yeast [1]. Mannans range from pure mannans containing only mannose to glucomannans and galactomannans comprised of mannosyl residues linked by various glucosidic linkages such as α-(1→2)-, α-(1→3)-, α-(1→6)-, β-(1→2)-, and/or β-(1→4)-links bonds [2,3]. The immunological properties of mannans are diverse, depending on their structures and source. N-linked and O-linked mannans derived from Candida albicans induce anti-fungal protective immunity [4]. Β-Galactomannans from soy appears to induce such anti-inflammatory properties [6]. These observations indicate that structures of mannosyl residues are an important factor determining the immunological properties of mannan

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