Yeast β-glucan is a well-established immunomodulatory agent. Studies have demonstrated that compared with vegetative yeast cells, β-glucan exposed on the surface of mutant yeast spores exhibits enhanced immunostimulatory effects. [Objective] To screen and identify yeast mutants with enhanced ability to activate the mammalian immune system. [Methods] Two yeast mutants (osw1Δ and mum3Δ) exposing β-glucan on the spore wall were constructed, and their immunostimulatory activity was evaluated via the macrophage stimulation assay and a mouse model. The role of the Dectin-1 signaling pathway was verified through small interfering RNA-mediated gene knockdown experiments. [Results] The spore lysates of osw1Δ and mum3Δ induced the production of inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in macrophages. Their immune activation was mainly dependent on the Dectin-1-mediated signaling pathway. In vivo studies showed that after oral administration of the osw1Δ spore lysate, the levels of IL-6 and TNF-α in the mouse serum increased by 1.8-fold and 1.7-fold, respectively, compared with those after oral administration of the wild-type spore lysate. Moreover, the osw1Δ spore lysate exerted a significant tumor-suppressive effect. [Conclusion] The spores of osw1Δ exhibit strong immune-activating effects. This mutant could be a candidate for the development of novel immunomodulators.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |