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Nature Communications Nov 2022Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite...
Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 on neutrophil-mediated antifungal immunity remains wholly unknown. Here, we show that the expression of PD-L1 on murine and human neutrophils was upregulated upon the engagement of C-type lectin receptor Dectin-1 with its ligand β-glucans, exposed on fungal pathogen Candida albicans yeast. Moreover, β-glucan stimulation induced PD-L1 translocation into nucleus to regulate the production of chemokines CXCL1 and CXCL2, which control neutrophil mobilization. Importantly, C. albicans infection-induced expression of PD-L1 leads to neutrophil accumulation in bone marrow, through mediating their autocrine secretion of CXCL1/2. Furthermore, neutrophil-specific deficiency of PD-L1 impaired CXCL1/2 secretion, which promoted neutrophil migration from bone marrow into the peripheral circulation, thereby conferring host resistance to C. albicans infection. Finally, either PD-L1 blockade or pharmacological inhibition of PD-L1 expression significantly increased neutrophil release from bone marrow to enhance host antifungal immunity. Our data together indicate that activation of Dectin-1/PD-L1 cascade by β-glucans inhibits neutrophil release from bone marrow reserve, contributing to the negative regulation of antifungal innate immunity, which functions as a potent immunotherapeutic target against life-threatening fungi infections.
Topics: Animals; Mice; Humans; Neutrophils; B7-H1 Antigen; Antifungal Agents; Bone Marrow; Candida albicans; beta-Glucans
PubMed: 36369287
DOI: 10.1038/s41467-022-34722-7 -
Molecules (Basel, Switzerland) Nov 2019The cell walls of fungi are composed of glycoproteins, chitin, and α- and β-glucans. Although there are many reports on β-glucans, α-glucan polysaccharides are not... (Review)
Review
The cell walls of fungi are composed of glycoproteins, chitin, and α- and β-glucans. Although there are many reports on β-glucans, α-glucan polysaccharides are not yet fully understood. This review characterizes the physicochemical properties and functions of (1→3)-α-d-glucans. Particular attention has been paid to practical application and the effect of glucans in various respects, taking into account unfavourable effects and potential use. The role of α-glucans in plant infection has been proven, and collected facts have confirmed the characteristics of infection associated with the presence of glucan in fungal cell wall. Like β-glucans, there are now evidence that α-glucans can also stimulate the immune system. Moreover, α-d-glucans have the ability to induce mutanases and can thus decompose plaque.
Topics: Aspergillosis; Aspergillus fumigatus; Cell Wall; Chitin; Fungi; Glucans; Glycoproteins; Plant Diseases; Polysaccharides; beta-Glucans
PubMed: 31684030
DOI: 10.3390/molecules24213972 -
Frontiers in Immunology 2023β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics.... (Review)
Review
β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics. β-glucan binds to various cell surface receptors, which produces an inflammatory response and accounts for its immune effects. A deeper comprehension of the processes by β-glucan recognizes its receptors, activates related signaling pathways, and regulates immunity as required. Such understanding will provide a basis for developing new therapies against . Herein, we briefly review the structural composition of β-glucans as a vital component of the cell wall, the host immunity mediated by β-glucans after their recognition, and discuss opportunities for the development of new strategies to combat .
Topics: Pneumocystis; beta-Glucans; Glucans; Pneumonia, Pneumocystis; Cell Wall
PubMed: 36845149
DOI: 10.3389/fimmu.2023.1094464 -
Microbiological Research Sep 2023β-glucans are a large class of complex polysaccharides found in abundant sources. Our dietary sources of β-glucans are cereals that include oats and barley, and... (Review)
Review
β-glucans are a large class of complex polysaccharides found in abundant sources. Our dietary sources of β-glucans are cereals that include oats and barley, and non-cereal sources can consist of mushrooms, microalgae, bacteria, and seaweeds. There is substantial clinical interest in β-glucans; as they can be used for a variety of diseases including cancer and cardiovascular conditions. Suitable sources of β-glucans for biopharmaceutical applications include bacteria, microalgae, mycelium, and yeast. Environmental factors including culture medium can influence the biomass and ultimately β-glucan content. Therefore, cultivation conditions for the above organisms can be controlled for sustainable enhanced production of β-glucans. This review discusses the various sources of β-glucans and their cultivation conditions that may be optimised to exploit sustainable production. Finally, this article discusses the immune-modulatory potential of β-glucans from these sources.
Topics: Humans; beta-Glucans; Agaricales; Immunity; Neoplasms; Saccharomyces cerevisiae; Pharmaceutical Preparations
PubMed: 37301079
DOI: 10.1016/j.micres.2023.127424 -
International Journal of Environmental... Nov 2021Waiting for an effective treatment against the SARS-CoV-2 virus (the cause of COVID-19), the current alternatives include prevention and the use of vaccines. At the... (Review)
Review
Waiting for an effective treatment against the SARS-CoV-2 virus (the cause of COVID-19), the current alternatives include prevention and the use of vaccines. At the moment, vaccination is the most effective strategy in the fight against pandemic. Vaccines can be administered with different natural biological products (adjuvants) with immunomodulating properties. Adjuvants can be taken orally, complementing vaccine action. Adjuvant compounds could play a key role in alleviating the symptoms of the disease, as well as in enhancing vaccine action. Adjuvants also contribute to an effective immune response and can enhance the protective effect of vaccines in immunocompromised individuals such as the elderly. Adjuvants must not produce adverse effects, toxicity, or any other symptoms that could alter immune system function. Vaccine adjuvants are substances of wide varying chemical structure that are used to boost the immune response against a simultaneously administered antigen. Glucans could work as adjuvants due to their immunomodulatory biological activity. In this respect, β-(1,3)-(1,6) glucans are considered the most effective and safe according to the list issued by the European Commission. Only glucans with a β-(1,3) bond linked to a β-(1,6) are considered modulators of certain biological responses. The aim of this review is to present the possible effects of β-glucans as adjuvants in the efficacy of vaccines against SARS-CoV-2 virus.
Topics: Adjuvants, Vaccine; Aged; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Vaccines; beta-Glucans
PubMed: 34886361
DOI: 10.3390/ijerph182312636 -
Molecules (Basel, Switzerland) Jun 2021The occurrence of microbial challenges in commercial poultry farming causes significant economic losses. Antibiotics have been used to control diseases involving... (Review)
Review
The occurrence of microbial challenges in commercial poultry farming causes significant economic losses. Antibiotics have been used to control diseases involving bacterial infection in poultry. As the incidence of antibiotic resistance turns out to be a serious problem, there is increased pressure on producers to reduce antibiotic use. With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of the chicken to resist microbial infection. Some β-glucans have been shown to improve gut health, to increase the flow of new immunocytes, increase macrophage function, stimulate phagocytosis, affect intestinal morphology, enhance goblet cell number and mucin-2 production, induce the increased expression of intestinal tight-junctions, and function as effective anti-inflammatory immunomodulators in poultry. As a result, β-glucans may provide a new tool for producers trying to reduce or eliminate the use of antibiotics in fowl diets. The specific activity of each β-glucan subtype still needs to be investigated. Upon knowledge, optimal β-glucan mixtures may be implemented in order to obtain optimal growth performance, exert anti-inflammatory and immunomodulatory activity, and optimized intestinal morphology and histology responses in poultry. This review provides an extensive overview of the current use of β glucans as additives and putative use as antibiotic alternative in poultry.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Immunologic Factors; Meat; Poultry; beta-Glucans
PubMed: 34200882
DOI: 10.3390/molecules26123560 -
Drug Metabolism and Pharmacokinetics Feb 2022Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main... (Review)
Review
Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main chain glucoses and the one nucleotide base. Dectin-1, one of the major receptors for β-glucans, is known to be expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells. This suggests that the above-mentioned complexes could deliver bound functional oligonucleotides (ODNs) including antisense (AS)-ODNs, small interfering RNA, and CpG-ODNs to the APCs. Analysis using a quartz crystal microbalance revealed that a complex consisting of SPG and dA with a phosphorothioate backbone was recognized by recombinant Dectin-1 protein. Treatment with this complex containing an AS-ODN for tumor necrosis factor alpha protected mice against lipopolysaccharide-induced hepatitis at a very low AS-ODN dose. Moreover, immunization with CpG-ODN/SPG complex and antigenic proteins induced potent antigen specific immune responses. The present review also represents peptide delivery by conjugation with dA and the preparation of a nanogel using DNA-DNA hybridization. These findings indicate that the delivery of a specific ODN using β-glucans could be used for treating various diseases caused by APCs and for activating antigen specific immune responses.
Topics: Animals; Antigen-Presenting Cells; Mice; Oligonucleotides; RNA, Small Interfering; Sizofiran; beta-Glucans
PubMed: 34896749
DOI: 10.1016/j.dmpk.2021.100434 -
Science Advances Sep 20231,3-β-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-β-glucan synthase located in the plasma membrane. This synthase is a...
1,3-β-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-β-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo-electron microscopy structure of 1,3-β-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A-type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-β-glucan synthase.
Topics: beta-Glucans; Cryoelectron Microscopy; Antifungal Agents; Catalysis
PubMed: 37703377
DOI: 10.1126/sciadv.adh7820 -
Nutrients Apr 2021The importance of a well-functioning and balanced immune system has become more apparent in recent decades. Various elements have however not yet been uncovered as... (Review)
Review
The importance of a well-functioning and balanced immune system has become more apparent in recent decades. Various elements have however not yet been uncovered as shown, for example, in the uncertainty on immune system responses to COVID-19. Fungal beta-glucans are bioactive molecules with immunomodulating properties. Insights into the effects and function of beta-glucans, which have been used in traditional Chinese medicine for centuries, advances with the help of modern immunological and biotechnological methods. However, it is still unclear into which area beta-glucans fit best: supplements or medicine? This review has highlighted the potential application of fungal beta-glucans in nutrition and medicine, reviewing their formulation, efficacy, safety profile, and immunomodulating effects. The current status of dietary fungal glucans with respect to the European scientific requirements for health claims related to the immune system and defense against pathogens has been reviewed. Comparing the evidence base of the putative health effects of fungal beta-glucan supplements with the published guidance documents by EFSA on substantiating immune stimulation and pathogen defense by food products shows that fungal beta-glucans could play a role in supporting and maintaining health and, thus, can be seen as a good health-promoting substance from food, which could mean that this effect may also be claimed if approved. In addition to these developments related to food uses of beta-glucan-containing supplements, beta-glucans could also hold a novel position in Western medicine as the concept of trained immunity is relatively new and has not been investigated to a large extent. These innovative concepts, together with the emerging success of modern immunological and biotechnological methods, suggest that fungal glucans may play a promising role in both perspectives, and that there are possibilities for traditional medicine to provide an immunological application in both medicine and nutrition.
Topics: Adolescent; Adult; Agaricales; Aged; Animals; COVID-19; Diet; Dietary Supplements; Female; Fungal Polysaccharides; Fungi; Humans; Immune System; Immunity; Immunomodulation; Infant; Infant, Newborn; Male; Middle Aged; Pleurotus; SARS-CoV-2; Saccharomyces cerevisiae; Young Adult; beta-Glucans
PubMed: 33920583
DOI: 10.3390/nu13041333 -
International Journal of Molecular... Mar 2022β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and... (Review)
Review
β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. β-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of β-glucans are deeply influenced by their molecular structure. This structure governs β-glucan interaction with multiple β-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of β-glucans to fully reveal their biological roles and potential applications. The deconstruction of β-glucans is a result of β-glucanase activity. In addition to being invaluable tools for the study of β-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for β-glucans and β-glucanases, and explore how their functionalities are dictated by their structure.
Topics: Fungi; Molecular Structure; Neoplasms; Plants; Polysaccharides; beta-Glucans
PubMed: 35328577
DOI: 10.3390/ijms23063156