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Bioscience Reports Jan 2024β-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of... (Review)
Review
β-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of β-glucans, such as water solubility, viscosity, molecular weight, and so on, have rendered them to be broadly applied in various food systems as well as in medicine to improve human health. Moreover, inhibition of cancer development could be achieved by an increase in immune system activity via β-glucans. β-glucans, which are part of a class of naturally occurring substances known as biological response modifiers (BRMs), have also shown evidence of being anti-tumorogenic, anti-cytotoxic, and anti-mutagenic. These properties make them attractive candidates for use as pharmaceutical health promoters. Along these lines, they could activate particular proteins or receptors, like lactosylceramide (LacCer), Dickin-1, complement receptor 3 (CR3), scavenge receptors (SR), and the toll-like receptor (TLR). This would cause the release of cytokines, which would then activate other antitumor immune cells, like macrophages stimulating neutrophils and monocytes. These cells are biased toward pro-inflammatory cytokine synthesis and phagocytosis enhancing the elicited immunological responses. So, to consider the importance of β-glucans, the present review introduces the structure characteristics, biological activity, and antitumor functions of fungal β-glucans, as well as their application.
Topics: Humans; beta-Glucans; Phagocytosis; Neutrophils; Macrophages; Cytokines
PubMed: 38088444
DOI: 10.1042/BSR20231686 -
Journal of Fungi (Basel, Switzerland) Jul 2023sp. are fungal pathogens and members of the Ascomycota phylum. Immunocompetent individuals can readily eliminate the fungus, whereas immunocompromised individuals can... (Review)
Review
sp. are fungal pathogens and members of the Ascomycota phylum. Immunocompetent individuals can readily eliminate the fungus, whereas immunocompromised individuals can develop pneumonia (PJP). Currently, over 500,000 cases occur worldwide, and the organism is listed on the recently released WHO fungal priority pathogens list. Overall, the number of PJP cases over the last few decades in developed countries with the use of highly effective antiretroviral therapy has decreased, but the cases of non-HIV individuals using immunosuppressive therapies have significantly increased. Even with relatively effective current anti- therapies, the mortality rate remains 30-60% in non-HIV patients and 10-20% during initial episodes of PJP in HIV/AIDS patients. Although the role of alveolar macrophages is well studied and established, there is also well-established and emerging evidence regarding the role of epithelial cells in the immune response to fungi. This mini review provides a brief overview summarizing the innate immune response of the lung epithelium and various continuously cultured mammalian cell lines to .
PubMed: 37504718
DOI: 10.3390/jof9070729 -
International Journal of Molecular... Jul 2023, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with...
, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with chronic airway diseases. Although knowledge pertaining to molecular mechanisms of host defense against NTM is increasing, macrophage receptors that recognize remain poorly defined. Dectin-1, a C-type lectin receptor identified as a fungal receptor, has been shown to be a pathogen recognition receptor (PRR) for both and NTM. To better understand the role of Dectin-1 in host defense against , we tested whether blocking Dectin-1 impaired the uptake of by human macrophages, and we compared pulmonary infection in Dectin-1-deficient and wild-type mice. Blocking antibody for Dectin-1 did not reduce macrophage phagocytosis of , but did reduce the ingestion of the fungal antigen zymosan. Laminarin, a glucan that blocks Dectin-1 and other PRRs, caused decreased phagocytosis of both and zymosan. Dectin-1-/- mice exhibited no defects in the control of infection, and no differences were detected in immune cell populations between wild type and Dectin-1-/- mice. These data demonstrate that murine defense against pulmonary infection, as well as ingestion of by human macrophages, can occur independent of Dectin-1. Thus, additional PRR(s) recognized by laminarin participate in macrophage phagocytosis of
Topics: Humans; Animals; Mice; Mycobacterium abscessus; Zymosan; Macrophages; Phagocytosis; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
PubMed: 37446240
DOI: 10.3390/ijms241311062 -
Journal of Clinical Medicine Feb 2024Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal... (Review)
Review
Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus . There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types and has shown an anti-proliferative activity, especially in leukemia, lymphoma, and myeloma lines. Moreover, research clarified the capability of molecules from to induce mitochondrial damage in acute promyelocytic leukemia cells, without cytotoxic effects in normal mononuclear cells. Active lipids extracted from the spores of this fungus have also been shown to induce apoptosis mediated by downregulation of P-Akt and upregulation of caspases-3, -8, and -9. Among in vivo studies, a study in BALB/c mice injected with WEHI-3 leukemic cells suggested that treatment with promotes differentiation of T- and B-cell precursors, phagocytosis by PBMCs, and NK cell activity. Our review presents data revealing the possibility of employing in hematological malignancies and incorporating it into clinical practice.
PubMed: 38398467
DOI: 10.3390/jcm13041153 -
Plant Physiology Dec 2023Recent breakthroughs in structural biology have provided valuable new insights into enzymes involved in plant cell wall metabolism. More specifically, the molecular...
Recent breakthroughs in structural biology have provided valuable new insights into enzymes involved in plant cell wall metabolism. More specifically, the molecular mechanism of synthesis of (1,3;1,4)-β-glucans, which are widespread in cell walls of commercially important cereals and grasses, has been the topic of debate and intense research activity for decades. However, an inability to purify these integral membrane enzymes or apply transgenic approaches without interpretative problems associated with pleiotropic effects has presented barriers to attempts to define their synthetic mechanisms. Following the demonstration that some members of the CslF sub-family of GT2 family enzymes mediate (1,3;1,4)-β-glucan synthesis, the expression of the corresponding genes in a heterologous system that is free of background complications has now been achieved. Biochemical analyses of the (1,3;1,4)-β-glucan synthesized in vitro, combined with 3-dimensional (3D) cryogenic-electron microscopy and AlphaFold protein structure predictions, have demonstrated how a single CslF6 enzyme, without exogenous primers, can incorporate both (1,3)- and (1,4)-β-linkages into the nascent polysaccharide chain. Similarly, 3D structures of xyloglucan endo-transglycosylases and (1,3;1,4)-β-glucan endo- and exohydrolases have allowed the mechanisms of (1,3;1,4)-β-glucan modification and degradation to be defined. X-ray crystallography and multi-scale modeling of a broad specificity GH3 β-glucan exohydrolase recently revealed a previously unknown and remarkable molecular mechanism with reactant trajectories through which a polysaccharide exohydrolase can act with a processive action pattern. The availability of high-quality protein 3D structural predictions should prove invaluable for defining structures, dynamics, and functions of other enzymes involved in plant cell wall metabolism in the immediate future.
Topics: beta-Glucans; Hydrolysis; Poaceae; Polysaccharides; Cell Wall
PubMed: 37594400
DOI: 10.1093/plphys/kiad415 -
Foods (Basel, Switzerland) Jul 2023Wheat bran (WB) consists mainly of different histological cell layers (pericarp, testa, hyaline layer and aleurone). WB contains large quantities of non-starch... (Review)
Review
Wheat bran (WB) consists mainly of different histological cell layers (pericarp, testa, hyaline layer and aleurone). WB contains large quantities of non-starch polysaccharides (NSP), including arabinoxylans (AX) and β-glucans. These dietary fibres have long been studied for their health effects on management and prevention of cardiovascular diseases, cholesterol, obesity, type-2 diabetes, and cancer. NSP benefits depend on their dose and molecular characteristics, including concentration, viscosity, molecular weight, and linked-polyphenols bioavailability. Given the positive health effects of WB, its incorporation in different food products is steadily increasing. However, the rheological, organoleptic and other problems associated with WB integration are numerous. Biological, physical, chemical and combined methods have been developed to optimise and modify NSP molecular characteristics. Most of these techniques aimed to potentially improve food processing, nutritional and health benefits. In this review, the physicochemical, molecular and functional properties of modified and unmodified WB are highlighted and explored. Up-to-date research findings from the clinical trials on mechanisms that WB have and their effects on health markers are critically reviewed. The review points out the lack of research using WB or purified WB fibre components in randomized, controlled clinical trials.
PubMed: 37509785
DOI: 10.3390/foods12142693 -
MBio Aug 2023To successfully induce disease, must effectively evade the host immune system. One mechanism used by to achieve this is to mask immunogenic β(1,3)-glucan epitopes...
To successfully induce disease, must effectively evade the host immune system. One mechanism used by to achieve this is to mask immunogenic β(1,3)-glucan epitopes within its cell wall under an outer layer of mannosylated glycoproteins. Consequently, induction of β(1,3)-glucan exposure (unmasking) genetic or chemical manipulation increases fungal recognition by host immune cells and attenuates disease during systemic infection in mice. Treatment with the echinocandin caspofungin is one of the most potent drivers of β(1,3)-glucan exposure. Several reports using murine infection models suggest a role for the immune system, and specifically host β(1,3)-glucan receptors, in mediating the efficacy of echinocandin treatment . However, the mechanism by which caspofungin-induced unmasking occurs is not well understood. In this report, we show that foci of unmasking co-localize with areas of increased chitin within the yeast cell wall in response to caspofungin, and that inhibition of chitin synthesis nikkomycin Z attenuates caspofungin-induced β(1,3)-glucan exposure. Furthermore, we find that both the calcineurin and Mkc1 mitogen-activated protein kinase pathways work synergistically to regulate β(1,3)-glucan exposure and chitin synthesis in response to drug treatment. When either of these pathways are interrupted, it results in a bimodal population of cells containing either high or low chitin content. Importantly, increased unmasking correlates with increased chitin content within these cells. Microscopy further indicates that caspofungin-induced unmasking correlates with actively growing cells. Collectively, our work presents a model in which chitin synthesis induces unmasking within the cell wall in response to caspofungin in growing cells. IMPORTANCE Systemic candidiasis has reported mortality rates ranging from 20% to 40%. The echinocandins, including caspofungin, are first-line antifungals used to treat systemic candidiasis. However, studies in mice have shown that echinocandin efficacy relies on both its cidal impacts on , as well as a functional immune system to successfully clear invading fungi. In addition to direct killing, caspofungin increases exposure (unmasking) of immunogenic β(1,3)-glucan moieties. To evade immune detection, β(1,3)-glucan is normally masked within the cell wall. Consequently, unmasked β(1,3)-glucan renders these cells more visible to the host immune system and attenuates disease progression. Therefore, discovery of how caspofungin-induced unmasking occurs is needed to elucidate how the drug facilitates host immune system-mediated clearance . We report a strong and consistent correlation between chitin deposition and unmasking in response to caspofungin and propose a model in which altered chitin synthesis drives increased unmasking during drug exposure.
Topics: Animals; Mice; Caspofungin; Candida albicans; Glucans; Chitin; Antifungal Agents; Echinocandins; Cell Wall; Lipopeptides
PubMed: 37377417
DOI: 10.1128/mbio.00074-23 -
Nature Communications Oct 2023Dimerization of C-type lectin receptors (CLRs) or Toll-like receptors (TLRs) can alter their ligand binding ability, thereby modulating immune responses. However, the...
Dimerization of C-type lectin receptors (CLRs) or Toll-like receptors (TLRs) can alter their ligand binding ability, thereby modulating immune responses. However, the possibilities and roles of dimerization between CLRs and TLRs remain unclear. Here we show that C-type lectin receptor-2d (CLEC2D) forms homodimers, as well as heterodimers with TLR2. Quantitative ligand binding assays reveal that both CLEC2D homodimers and CLEC2D/TLR2 heterodimers have a higher binding ability to fungi-derived β-glucans than TLR2 homodimers. Moreover, homo- or hetero-dimeric CLEC2D mediates β-glucan-induced ubiquitination and degradation of MyD88 to inhibit the activation of transcription factor IRF5 and subsequent IL-12 production. Clec2d-deficient female mice are resistant to infection with Candida albicans, a human fungal pathogen, owing to the increase of IL-12 production and subsequent generation of IFN-γ-producing NK cells. Together, these data indicate that CLEC2D forms homodimers or heterodimers with TLR2, which negatively regulate antifungal immunity through suppression of IRF5-mediated IL-12 production. These homo- and hetero-dimers of CLEC2D and TLR2 provide an example of receptor dimerization to regulate host innate immunity against microbial infections.
Topics: Animals; Female; Humans; Mice; Antifungal Agents; beta-Glucans; Immunity, Innate; Interferon Regulatory Factors; Interleukin-12; Lectins, C-Type; Ligands; Toll-Like Receptor 2; Toll-Like Receptors
PubMed: 37872182
DOI: 10.1038/s41467-023-42216-3 -
Frontiers in Immunology 2024cell wall component β-glucan has been extensively studied for its ability to induce epigenetic and functional reprogramming of innate immune cells, a process termed ....
cell wall component β-glucan has been extensively studied for its ability to induce epigenetic and functional reprogramming of innate immune cells, a process termed . We show that a high-complexity blend of two individual β-glucans from possesses strong bioactivity, resulting in an enhanced trained innate immune response by human primary monocytes. The training required the Dectin-1/CR3, TLR4, and MMR receptors, as well as the Raf-1, Syk, and PI3K downstream signaling molecules. By activating multiple receptors and downstream signaling pathways, the components of this β-glucan preparation are able to act synergistically, causing a robust secondary response upon an unrelated challenge. In murine models of melanoma and bladder cell carcinoma, pre-treatment of mice with the β-glucan preparation led to a significant reduction in tumor growth. These insights may aid in the development of future therapies based on β-glucan structures that induce an effective trained immunity response.
Topics: Humans; Animals; Mice; Saccharomyces cerevisiae; Trained Immunity; beta-Glucans; Monocytes; Signal Transduction
PubMed: 38415247
DOI: 10.3389/fimmu.2024.1323333 -
Medical Mycology Jul 2023The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold... (Meta-Analysis)
Meta-Analysis
The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.
Topics: Animals; Fusariosis; beta-Glucans; Invasive Fungal Infections; Sensitivity and Specificity
PubMed: 37381179
DOI: 10.1093/mmy/myad061