Exopolysaccharides extracted from submerged cultures of Ganoderma lucidumactivate the NLRP3 inflammasome

Interleucin-1β (IL-1β) is a pivotal cytokine in pro-inflammatory response induction, and it is regarded as protective in various diseases. IL-1β secretion is mainly associated with activation of the inflammasome complex, which generally is tightly regulated, depending on two signals for significant activity. The water-insoluble fraction of the mushroom Ganoderma lucidum was extracted and co-cultivated with murine bone marrow macrophages. We demonstrated that G. lucidum exopolysaccharides (EPS) could induce IL-1β production and release in murine macrophages. The mechanisms underlying EPS-induced priming encompass recognition through dectin-1 and activation of the spleen tyrosine kinase (Syk) / nuclear factor kappa-light-chain-enhancer of the activated B (NF-kB) axis. In addition, EPS stimulates IL-1β secretion in a phagocytosis-dependent manner via the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in response to reactive oxygen species production, potassium efflux, phagolysosomal acidification, and cathepsin B release. Both caspase-1 and, to a lesser extent, caspase-8 were activated upon EPS stimulus and required for IL-1β cleavage and release. The treatment with EPS by gavage of Cryptococcus neoformans-infected mice showed increased survival. Our study highlighted significant stimulation by G. lucidum EPS to innate immune cells, suggesting a potential adjuvant in antimicrobial treatment schemes.