Immunoregulatory activity of a low-molecular-weight heteropolysaccharide from Ganoderma leucocontextum fruiting bodies in vitro and in vivo

•GLP-1 could be recognized by TLR2 and dectin-1 receptors in RAW264.7 macrophages.•GLP-1 enhanced phagocytic activity and promoted ROS, NO, and cytokines production.•The molecular mechanism related to the immunoregulatory effect of GLP-1 was elucidated.•GLP-1 improved immune functions in cyclophosphamide-induced immunosuppressed mice. The chemical structure of GLP-1, a novel water-soluble heteropolysaccharide purified Ganoderma leucocontextum fruiting bodies, has been characterized in our previous study. This study aimed to investigate the immunostimulatory activity of GLP-1 in vitro and in vivo by using RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice model. Results showed that GLP-1 was able to enhance phagocytic activity and promote the production of reactive oxygen species, nitric oxide, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 in RAW264.7 macrophages. Moreover, GLP-1 could activate mitogen-activated protein kinase, phosphatidylinositol-3-kinase/protein kinase B, and nuclear factor-kappa B signaling pathways through toll-like receptor 2 and dectin-1 receptors. Furthermore, GLP-1 increased the thymus index, serum immunoglobulin levels, and percentage of CD3+ T lymphocytes in cyclophosphamide-induced immunosuppressed mice. These results demonstrated that GLP-1 possessed significant immunostimulatory effects in vivo and in vitro and could be developed as an effective immunomodulator for application in functional foods.