Abstract
β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils, and natural killer cells. The characteristics of the immune responses generated depend on the cell types and receptors involved. Size and biochemical composition of β-glucans isolated from different sources affect their immunomodulatory properties. The variety of studies using crude extracts of fungal cell wall rather than purified β-glucans renders data difficult to interpret. A better understanding of the mechanisms of purified fungal β-glucan recognition, downstream signaling pathways, and subsequent immune regulation activated, is, therefore, essential not only to develop new antifungal therapy but also to evaluate β-glucan as a putative anti-infective and antitumor mediator. Here, we briefly review the complexity of interactions between fungal β-glucans and mononuclear phagocytes during fungal infections. Furthermore, we discuss and present available studies suggesting how different fungal β-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes, which make them potential candidates as therapeutic agents.
Highlights
Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Fungal β-glucans, that represent the most abundant polysaccharides found in the cell wall of fungi, β-Glucan in Health and Disease are mainly characterized by the presence of β(1,6)-linked branches coming off of the β(1,3) backbone
Β-glucans as the most abundant fungal cell wall polysaccharide in human fungal pathogens, is a key pathogen-associated molecular pattern (PAMP) that is detected upon fungal infection to trigger the host immune responses in vertebrates and invertebrates [7]
Summary
Β-glucans are naturally occurring glucose polymers that are present in abundance in plants, bacteria, and fungi. Fungal β-glucans, that represent the most abundant polysaccharides found in the cell wall of fungi, β-Glucan in Health and Disease are mainly characterized by the presence of β(1,6)-linked branches coming off of the β(1,3) backbone. Β-glucans of mushrooms have short β(1,6)-linked branches whereas those of yeast have β(1,6)-side branches with additional β(1,3) regions [5] Of note, these structural differences may influence the immunogenic properties of β-glucans and many studies have suggested that a higher degree of structural complexity is associated with enhanced β-glucans-induced antimicrobial and anticancer activities [6]. A systematic investigation of the receptor binding, the signaling pathway, and the activated immune responses induced by pure β-glucans with known structure is, needed to better understand the fungal pathogenesis and to effectively apply the use of the β-glucan for the treatment of cancer and infectious diseases. We will explore the effects of fungal β-glucan treatment on cancer and infectious diseases and discussed the recently described innate immune memory of monocytes associated with β-glucans training
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