Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1

During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. beta-Glucans are glucose polymers of a linear beta(1,3)-glucan backbone with beta(1,6)-linked side chains. The immunostimulatory and antitumor activities of beta-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate beta-glucans, despite their large size, can be taken up by the M cells of Peyer's patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled beta-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of beta-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of beta-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of beta-glucan contributes to its immunostimulating effect in hosts and the potential uses of beta-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of (beta-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.