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Graphical abstract Highlights: • Fusarium solani DO7 was isolated from the stem of Dendrobium officinale. • A novel polysaccharide DG2 was isolated from F. solani DO7. • DG2 showed no toxicity to human embryonic kidney cells and RAW 264.7 cells. • DG2 possesses higher immune enhancement activity. • DG2 had good potential as functional food candidate. Abstract A novel polysaccharide DG2 was obtained from the Dendrobium officinale endophytic fungus Fusarium solani DO7. The structural characterization and immunological activity of DG2 were investigated. Results showed that DG2 with the molecular weight of 152.8 kDa was composed of Gal p , Man p , Glc p and Ara f at a molar ratio of 4.3:1.9:2.8: 1.0. The main linkage types of DG2 were (1 →)-β-D-Glc, (1 → 4)-β-D-Glc, (1 → 3,6)-β-D-Gal and (1 → 6)-β-D-Gal, which demonstrated DG2 was a novel galactoglucan and different from other fungal and botanic polysaccharide. Furthermore, DG2 did not contain deoxynivalenol, and showed no direct toxicity to human embryonic kidney cells and RAW 264.7 cells. Meanwhile, DG2 could increase the TNF-α, IL-6 and iNOs mRNA expression levels of RAW264.7 cells, and further promote the production of TNF-α, IL-6 and NO. These results suggested DG2 could enhance macrophage-mediated immune responses and have the potential to be an attractive functional food supplement candidate for the hypoimmunity therapies. [ABSTRACT FROM AUTHOR]