Journal of Immunology and Immunopathology

Trained immunity is a phenomenon of innate immune memory that confers enhanced protection against secondary infections. β-glucans are natural polysaccharides derived from various sources, such as fungi, bacteria, plants, and algae, that have been shown to induce trained immunity in different animal species, such as cattle, buffalo, dog, fish, and poultry. β-glucans bind to various receptors on the surface of innate immune cells, such as dectin-1, complement receptor 3 (CR3), toll-like receptor 2 (TLR2), and scavenger receptor A (SR-A), and trigger intracellular signalling cascades that lead to the activation of transcription factors, such as nuclear factor kappa B (NF- κB), interferon regulatory factor (IRF), and signal transducer and activator of transcription (STAT), which regulate the expression of genes involved in immune responses. β-glucans also induce the production of cytokines, such as interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF- α), and interferon gamma (IFN- γ), which act as autocrine or paracrine factors that amplify and sustain the trained immunity phenotype. β- glucans also induce metabolic reprogramming of innate immune cells by shifting their energy and biosynthetic pathways from oxidative phosphorylation to glycolysis and pentose phosphate pathway, which provide more ATP and NADPH for cellular activation and survival. β-glucans also increase the production of reactive oxygen species (ROS) and nitric oxide (NO), which act as signalling molecules that modulate the epigenetic and transcriptional reprogramming of innate immune cells. β-glucans also affect the lipid metabolism of innate immune cells by increasing the synthesis of cholesterol and fatty acids, which are essential for membrane fluidity and signalling. β-glucans have potential applications in immunotherapy for various diseases and conditions, such as viral infections, inflammatory disorders, and cancer. This review summarises the current knowledge on the sources, structures, receptors, and mechanisms of β-glucans as immunomodulators of trained immunity in different animal species.