β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors

C Fernández-Lainez,R Akkerman,M.M.P Oerlemans,M.J Logtenberg,H.A Schols,L.A Silva-Lagos,G López-Velázquez,P De Vos

doi:10.1016/j.carbpol.2021.118893

Abstract

Graminan-type fructans (GTFs) have demonstrated immune benefits. However, mechanisms underlying these benefits are unknown. We studied GTFs interaction with Toll-like receptors (TLRs), performed molecular docking and determined their impact on dendritic cells (DCs). Effects of GTFs were compared with those of inulin-type fructans (ITFs). Whereas ITFs only contained β(2→1)-linked fructans, GTFs showed higher complexity as it contains additional β(2→6)-linkages. GTFs activated NF-κB/AP-1 through MyD88 and TRIF pathways. GTFs stimulated TLR3, 7 and 9 while ITFs activated TLR2 and TLR4. GTFs strongly inhibited TLR2 and TLR4, while ITFs did not inhibit any TLR. Molecular docking demonstrated interactions of fructans with TLR2, 3, and 4 in a structure dependent fashion. Moreover, ITFs and GTFs attenuated pro-inflammatory cytokine production of stimulated DCs. These findings demonstrate immunomodulatory effects of GTFs via TLRs and attenuation of cytokine production in dendritic cells by GTFs and long-chain ITF.

Highlights

Economic progress has led to spreading of the Western life style which has contributed to an increased risk for development of noncommunicable diseases such as cardiovascular diseases, stroke, cancer, diabetes and respiratory diseases (Beaglehole et al, 2011; Patry & Nagler, 2021)
Inulin and graminan-type fructans were analyzed for determination of their molecular weight distribution profiles and the components that make up the mixtures
We show that Graminan-type fructans (GTFs) especially stimulate Toll-like receptors (TLRs) 3, 7 and 9 while they were able to inhibit TLR2 and TLR4

Summary

Introduction

Economic progress has led to spreading of the Western life style which has contributed to an increased risk for development of noncommunicable diseases such as cardiovascular diseases, stroke, cancer, diabetes and respiratory diseases (Beaglehole et al, 2011; Patry & Nagler, 2021). These changes in lifestyle include less physical activity, higher intake of processed foods enriched with animal fats as well as lower intake of dietary fibers compared to more traditional diets (Health & Services, 2015; Temba et al, 2021).

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