"β-glucan signalling stimulates NOX-2 dependent autophagy and LC-3 associated autophagy (LAP) pathway"

β-Glucan, a complex polysaccharide derived from fungal and yeast cell walls, plays a crucial role in modulating immune responses through their interaction with receptors such as Dectin-1 and Complement receptor 3 (CR-3). This review provides an in-depth analysis of the molecular mechanisms by which β-glucans activate receptor-mediated signalling pathways, focusing particularly on the LC3-associated phagocytosis (LAP) and autophagy pathways. Hence, we explore how β-glucan receptor engagement stimulates NADPH oxidase 2 (NOX-2), leading to the intracellular production of significant level of reactive oxygen species (ROS) essential for both conventional autophagy and LAP. While significant progress has been made in elucidation of downstream signaling by glucans, the regulation of phago-lysosomal maturation and antigen presentation during LAP induction still remains less explored. This review aims to provide a comprehensive overview of these pathways and their regulation by β-glucans. By consolidating the current knowledge, we seek to highlight how these mechanisms can be leveraged for therapeutic applications, particularly in the context of tuberculosis (TB) management, where β-glucans could serve as host-directed adjuvant therapies to combat drug-resistant strains. Despite major advancements in this field, currently key research gaps still persist, including detailed molecular interactions between β-glucan receptors and NOX-2 and the translation of these findings to in-vivo models and clinical investigations. This review underscores the need for further research to explore the therapeutic potential of β-glucans in managing not only tuberculosis but also other diseases such as cancer, cardiovascular conditions, and metabolic disorders.