TY - JOUR
T1 - β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors
AU - Fernández-Lainez, C.
AU - Akkerman, R.
AU - Oerlemans, M.M.P.
AU - Logtenberg, M.J.
AU - Schols, H.A.
AU - Silva-Lagos, L.A.
AU - López-Velázquez, G.
AU - de Vos, P.
PY - 2022
Y1 - 2022
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 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.
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 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.
KW - Branched-chain fructans
KW - Functional food
KW - Immunomodulation
KW - Non-digestible carbohydrates
KW - Toll-like receptors
U2 - 10.1016/j.carbpol.2021.118893
DO - 10.1016/j.carbpol.2021.118893
M3 - Article
AN - SCOPUS:85119426317
SN - 0144-8617
VL - 277
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
M1 - 118893
ER -