Ganoderma lucidum polysaccharides and their immunomodulatory effects via the Dectin-1/NF-κB signaling axis

Ganoderma lucidum polysaccharides (GLPs), the core bioactive macromolecules of Ganoderma lucidum, have garnered massive research attention for their robust immunomodulatory effects. Cumulative data verify that GLP β-glucans specifically bind pattern recognition receptor Dectin-1, alongside auxiliary co-receptors for synergistic regulation. Dectin-1 engagement triggers the Syk-CARD9 cascade, promoting NF-κB nuclear translocation to upregulate immune genes and directly regulate macrophage polarization and dendritic cell maturation via Dectin-1, which in turn indirectly activates NK cells and T cells through cytokine release (IL-12, IL-18) and antigen presentation by matured dendritic cells. This review details GLP structural characteristics and corresponding structure-immunomodulation relationships, highlighting the pivotal Dectin-1/NF-κB signaling axis. It summarizes state-of-the-art GLP research in anti-tumor, anti-inflammatory therapy and immune homeostasis, clarifies molecular mechanisms, sorts preclinical outcomes, and addresses obstacles limiting clinical translation. GLPs are classified by raw sources, extraction protocols, molecular weight, monosaccharide components, glycosidic linkages and spatial conformations; each structural trait is paired with dedicated characterization and cell/animal verification assays to eliminate superficial structure-activity generalizations. This work lays theoretical groundwork for fungal polysaccharide immunomodulator preclinical development, yet human clinical trials remain indispensable.