TY - JOUR
T1 - β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors
AU - Fernandez-Lainez, C.
AU - Akkerman, R.
AU - Oerlemans, M. M. P.
AU - Logtenberg, M. J.
AU - Schols, H. A.
AU - Silva-Lagos, L. A.
AU - Lopez-Velazquez, G.
AU - de Vos, P.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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 beta(2 -> 1)-linked fructans, GTFs showed higher complexity as it contains additional beta(2 -> 6)-linkages. GTFs activated NF-kappa B/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.
AB - 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 beta(2 -> 1)-linked fructans, GTFs showed higher complexity as it contains additional beta(2 -> 6)-linkages. GTFs activated NF-kappa B/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.
KW - Branched-chain fructans
KW - Functional food
KW - Immunomodulation
KW - Non -digestible carbohydrates
KW - Toll -like receptors
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=researchintelligenceproject&SrcAuth=WosAPI&KeyUT=WOS:000761088700006&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.carbpol.2021.118893
DO - 10.1016/j.carbpol.2021.118893
M3 - Article
C2 - 34893295
SN - 0144-8617
VL - 277
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
M1 - 118893
ER -