Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de México, Mexico; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México UNAM, Ciudad de México, Mexico.
Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
Carbohydr Polym. 2022 Feb 1;277:118893. doi: 10.1016/j.carbpol.2021.118893. Epub 2021 Nov 15.
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.
格兰坦型果聚糖（GTFs）具有免疫益处。然而，这些益处的机制尚不清楚。我们研究了 GTFs 与 Toll 样受体（TLRs）的相互作用，进行了分子对接，并确定了它们对树突状细胞（DCs）的影响。将 GTFs 的作用与菊粉型果聚糖（ITFs）进行了比较。虽然 ITFs 仅含有β（2→1）-连接的果聚糖，但 GTFs 具有更高的复杂性，因为它还含有额外的β（2→6）-键。GTFs 通过 MyD88 和 TRIF 途径激活 NF-κB/AP-1。GTFs 刺激 TLR3、7 和 9，而 ITFs 激活 TLR2 和 TLR4。GTFs 强烈抑制 TLR2 和 TLR4，而 ITFs 不抑制任何 TLR。分子对接表明果聚糖与 TLR2、3 和 4 以结构依赖的方式相互作用。此外，ITFs 和 GTFs 减弱了刺激的 DCs 中促炎细胞因子的产生。这些发现表明 GTFs 通过 TLRs 发挥免疫调节作用，并通过 GTFs 和长链 ITF 减弱树突状细胞中细胞因子的产生。
