Critical review on signaling pathways of immune boosting effects of edible and medicinal mushrooms

Edible and medicinal mushrooms have been used for both culinary and medicinal purposes since ancient times, as they offer a broad range of therapeutic benefits in immune function and immune responses enhancement via various major signaling pathways. The major signaling pathways involved are the TLR signaling pathway, MAPK signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, Ca 2+/ Calcineurin/NFAT signaling pathway, and Dectin-1 signaling pathway. The species-specific, unique-structured, and varying concentration of bioactive compounds present in edible and medicinal mushrooms, such as polysaccharides (mainly β -glucans), terpenoids, lectins, and fungal immunomodulatory proteins (FIPs), play a pivotal role in immune modulation activities via above mentioned signaling pathways. These natural immunomodulators strengthen the body's defense mechanisms, leading to long-term well-being and a healthy lifestyle. These immunomodulators can be immunosuppressants, immunostimulants, or immunoadjuvants, which allow mushrooms to function during autoimmune diseases as well as to boost the immune system via innate and adaptive immunity. Generally, the immunomodulating metabolites in the mushrooms initiate the cellular signaling pathways mainly through binding to pattern recognition receptors (PRRs) found on the surface of immune cells such as macrophages and dendritic cells, which will then subsequently trigger upstream and downstream signaling cascades. This leads to enhanced phagocytosis and cytotoxic activity in natural killer cells (NK cells), activation, proliferation, differentiation, and maturation of T and B lymphocytes. Furthermore, these activated signaling pathways influence the production of key signaling proteins, such as cytokines and chemokines. This review summarizes the molecular mechanism of edible and medicinal mushrooms in immune-boosting effects through regulating multiple signaling pathways.