Short Lecture "Water-soluble heteropolysaccharides from medicinal plants and fungi interact with toll-like receptors"

Naturally derived polysaccharides have the potential to trigger pattern recognition receptors (PRRs) on the surface of macrophages, thereby initiating an innate inflammatory immune response. When properly activated, macrophages can kill cancer cells, secrete cytokines for immune cell recruitment to tumors, and stimulate T cells to fight cancer metastases. Therefore, macrophages are attractive targets for novel antitumor immunotherapy drugs. We have recently identified polysaccharides from the medicinal fungus I. obliquus (Chaga) that were agonists of toll-like receptor 2 (TLR2), TLR4, and Dectin-1a, and able to elicit a tumoricidal pro-inflammatory response in macrophages. We are currently investigating further at how these polysaccharides from I. obliquus bind to several PRRs and its consequence for macrophage activation. We are also screening novel water-soluble polysaccharides isolated from selected medicinal plants from Norway and Brazil for their ability to activate macrophages and for their potential use in cancer treatment. These include a heterogenous group of pectins, xylans and arabinogalactan-proteins among others. To identify polysaccharides of potential interest for immunotherapy, we take advantage of human embryonic kidney (HEK293) blue reporter cell lines transfected with specific PRRs (TLR2, TLR2-TLR6, TLR4, TLR3, Mincle, Dectin-1a and Dectin-1b). The ability of a single polysaccharide to bind to several PRRs opens the possibility of simultaneous activation of multiple receptors, thus leading to a potential synergistic effect. Further research on the active isolates will seek to demonstrate such a synergistic macrophage activation by polysaccharides, as well as structure-activity relationship through enzymatic degradation.

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Artikel online veröffentlicht:
16. November 2023