As a natural barrier of the human body, the immune system has the functions of immune surveillance, defense, and regulation. It can be divided into adaptive immunity and innate immunity. The former is subdivided into cellular immunity and humoral immunity, which are respectively exerted by T lymphocytes and B lymphocytes, and the latter is mainly exerted by innate immune cells, such as monocyte macrophages and natural killer (NK) cells [58]. Therefore, modern medicine mainly evaluates immune function from four aspects: cellular immunity, humoral immunity, mononuclear macrophage phagocytosis, and NK cell activity. Carbohydrates are common surface molecules in biological systems. Due to their rich structural diversity, carbohydrate molecules play an important role in cell recognition and signal transduction, including immune recognition and activation [59,60]. Furthermore, (1→3)-β-glucan is a polysaccharide adjuvant widely existing in bacterial and fungal cell walls, which can stimulate antibacterial immune response [60]. In the 1950s, Dr. Pillemer first discovered and reported that there was a substance in the yeast cell wall that could improve immunity [61]. In later research, Diluzio’s group discovered that the immunity-boosting substance in the yeast cell wall was (1→3)-β-glucan, isolated from baker’s yeast [62,63].

Yeast (1→3)-β-glucan activates various immune cells, including macrophages and neutrophils, leading to increased production of interleukin (IL), cytokinin, and special antibodies. This comprehensive stimulation of the immune system prepares the body to better fight against diseases [64,65]. In addition, yeast (1→3)-β-glucan restores the ability of lymphocytes to produce cytokines such as IL-1 and effectively regulates immune function [66,67,68]. Many experiments have indicated that yeast (1→3)-β-glucan promotes the production of IgM antibodies, improving humoral immunity. Moreover, yeast (1→3)-β-glucan activates toll-like receptor 2 (TLR2), inducing nuclear factor (NF)- κB activation and tumor necrosis factor (TNF)-α secretion, as well as regulatory antigen-presenting cells and immune tolerance [69,70]. The yeast (1→3)-β-glucan-activated cells stimulate the host’s non-specific defense mechanism and are thus being studied for their potential in cancer, infectious disease, and wound treatment. In 2008, β-glucan extracted from S. cerevisiae’s yeast was released by the US Food and Drug Administration (FDA) as a safe food ingredient that can be added to general food. It is a very rare active immune substance, which can kill harmful viruses and maintain good immunity. Many years ago, National Aeronautics and Space Administration (NASA) listed yeast glucan as a food for astronauts to enhance their immunity.

Many researchers have not only demonstrated the regulatory effect of yeast (1→3)-β-glucan on immunity, such as induction of autoimmune arthritis or enhancement of nitric oxide (NO) synthesis, through in vitro cell experiments or in vivo experiments in mice, respectively [71,72,73], but also showed that β-glucan also has the effect of immune stimulation on zebrafish [74,75].

Wu et al. reported that the addition of (1→3)-β-glucan can also lessen the inflammatory response after lipopolysaccharide (LPS) stress [76]. Yeast (1→3)-β-glucan is also an important enhancer of mucosal immunity in the digestive tract [77]. The digestive system is the primary point of contact for many pathogens and foreign substances, and mucosal immunity in the system plays a vital role in defending against these threats. Additionally, it has also been found that (1→3)-β-glucan can improve the level of lysozyme in animal serum and the antibody titer [78]. Yeast (1→3)-β-glucan can activate neutrophils and phagocytes in gastrointestinal tissues, thereby further activating and affecting the “immune nerve endocrine” regulatory network, enhancing its anti-infection, anti-stress, and cellular adaptive protection capabilities and also enhancing macrophage-mediated tissue repair, accelerating the repair process of ulcers, and improving the repair quality [79]. Yeast β-glucan has the ability to bind with surface receptors of macrophages, neutrophils, and lymphocytes, which can affect the cellular signaling process, activate the immune activity of lymphocytes, and enable them to swiftly reach the site of infection [80]. It acts as an immune response booster and facilitates whey protein. Whey protein is a high-quality protein that contains all of the essential amino acids needed by the body. Combining with β-glucan, it can activate immune cells. While whey protein provides the building blocks necessary for these cells to function properly, they can work synergistically to enhance the immune response [81]. The latest research found that pre-treatment of mice with (1→3)-β-glucan can reduce the growth of tumors and elucidated that β-glucan transcriptomically and epigenetically rewires granulopoiesis and reprograms neutrophils towards an anti-tumor phenotype to form a long-term innate immune memory, i.e., trained immunity. Moreover, the anti-tumor effects of (1→3)-β-glucan-induced trained immunity can be transferred to recipient initial mice via bone marrow transplantation [82]. Furthermore, (1→3)-β-glucan can stimulate the innate immunity of Pagrus auratus by enhancing the respiratory burst of macrophages [83]. Besides for humans, Chang et al. also showed that the addition of (1→3)-β-glucan to the diet of shrimp enhanced the bacteriophage activity of blood cells, cell adhesion, and production of reactive oxygen species [84].

Macrophages are essential to every stage of host defense and are engaged in both innate and adaptive immune responses in case of infection. The pathogen crosses the epithelial barrier, following phagocytosis by macrophages and digestion by lysosomal enzymes, which are important processes for presenting antigens from the pathogens as phagocytic activity, and lysosomal enzymes determine the function of macrophages [85]. The secretion of cytokines (IL-1, IL-6, IL-8, IL-12, TNF-a) and inflammatory mediators (NO, hydrogen peroxide (H₂O₂)) are also the downstream effect of these cells. Thus, β-glucan-activated macrophage function enhances host immune defense (Figure 1) [86,87]. Furthermore, (1→3)-β-Glucan is an effective immunomodulator [88,89,90], which can enhance the anti-tumor activity of peritoneal macrophages. In vitro studies showed that the killing effect of monocytes and neutrophils on microorganisms in healthy volunteers was enhanced after taking (1→3)-β-glucan. In addition to activating macrophages, T cells, and natural killer (NK) cells, (1→3)-β-glucan also activates complement components through a selective activation pathway. When (1→3)-β-glucan is present, it can bind to complement component C3, which triggers a cascade of reactions leading to the activation of the alternative pathway. This results in the formation of the C3 convertase enzyme, which cleaves C3 into iC3b. iC3b then binds to the surface of the pathogen, marking it for destruction by immune cells [5,6]. Activation of complement components through this pathway is important because it allows for a more targeted response to pathogens, without causing excessive inflammation or tissue damage. Vaccine adjuvants have a variety of mechanisms, typically including storage effects, promoting antigen presentation, increasing the secretion of immunomodulatory cytokines to control cellular responses with T and B, stimulating innate immunity, and indirectly modulating adaptive immune responses [91]. At present, (1→3)-β-glucan is an attractive candidate for immune adjuvants and is used in a wide range of vaccine development. It can activate the immune system and induce the Th1 immune response [92,93]. The potential effects of (1→3)-β-glucan as an adjuvant on the effectiveness of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus vaccination were discussed by Alfredo’s group (Figure 1) [94].