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  3. Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response

Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response

  • Carbohydr Polym. 2023 Apr 1;305:120533. doi: 10.1016/j.carbpol.2022.120533.
Mingzhi Li 1,  Xiaojun Huang 1,  Jiajia Wen 1,  Shikang Chen 1,  Xincheng Wu 1,  Wanning Ma 1,  Steve W Cui 2,  Mingyong Xie 1,  Shaoping Nie 3
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: [email protected].
PMID: 36737186 DOI: 10.1016/j.carbpol.2022.120533
Abstract

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.

Keywords

Glucomannans; Innate immune receptors; Mannose receptor; Multi-pathway; Synergistic; TLR4-MD2.

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