State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China; Agriculture and Agri-Food Canada, Guelph Research and Development Centre, 93 Stone Road West, Guelph, Ontario NIG 5C9, Canada.
Carbohydr Polym. 2023 Apr 1;305:120533. doi: 10.1016/j.carbpol.2022.120533. Epub 2023 Jan 4.
The law and mechanism of the interaction between polysaccharides and pattern recognition receptors (PRRs) has been unclear. Herein, three glucomannans with different structures were selected to explore the universal mechanism for PRRs to recognize glucomannans. Screening results showed that the silence of TLR4 but not TLR2 severely blocked the production of inflammatory cytokines and the transduction of signal pathways. In-depth results revealed that the participation of myeloid differentiation protein 2 (MD2) and CD14 and the dimerization of the TLR4-MD2 complex were required for glucomannan-activated TLR4 signal transduction. Mannose receptor (MR) was also engaged in glucomannan-induced respiratory burst, endocytosis, and inflammatory signaling pathways in a spleen tyrosine kinase-dependent manner. The internalization of glucomannans into the cytoplasm by MR directly initiated complex intracellular signaling cascades. Finally, molecular docking characterized the binding energy and binding sites between glucomannans and multiple receptors from other perspectives. The essence of glucomannans recognized by PRRs was the non-covalent interaction of multiple receptors and the subsequent transmission of the signal cascade was triggered in a multi-channel and cooperative manner. As a result, the hypothesis that "Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response" was proposed to outline these meaningful phenomena.
多糖与模式识别受体（PRRs）相互作用的规律和机制尚不清楚。本文选择三种结构不同的葡甘露聚糖，以探索 PRRs 识别葡甘露聚糖的普遍机制。筛选结果表明，TLR4 而非 TLR2 的沉默严重阻断了炎症细胞因子的产生和信号通路的转导。深入的结果表明，髓样分化蛋白 2（MD2）和 CD14 的参与以及 TLR4-MD2 复合物的二聚化是葡甘露聚糖激活 TLR4 信号转导所必需的。甘露糖受体（MR）也通过脾酪氨酸激酶依赖性参与葡甘露聚糖诱导的呼吸爆发、内吞作用和炎症信号通路。MR 将葡甘露聚糖内化到细胞质中，直接引发复杂的细胞内信号级联反应。最后，分子对接从多个角度描述了葡甘露聚糖与多种受体之间的结合能和结合位点。PRRs 识别的葡甘露聚糖的本质是多个受体的非共价相互作用，随后以多通道和协作的方式触发信号级联的传递。因此，提出了“先天免疫受体对多糖的共同识别引发多途径协同免疫反应”的假设，以描述这些有意义的现象。
