Chitin, Chitinase Responses, and Invasive Fungal Infections
01 Jan 2012-International Journal of Microbiology (Hindawi Publishing Corporation)-Vol. 2012, pp 920459-920459
TL;DR: The mechanisms of host chitinase responses may have implications for diagnostic assays as well as novel therapeutic approaches for patients that are at risk of contracting fatal fungal infections.
Abstract: The human immune system is capable of recognizing and degrading chitin, an important cell wall component of pathogenic fungi. In the context of host-immune responses to fungal infections, herein we review the particular contributions and interplay of fungus and chitin recognition, and chitin-degrading enzymes, known as chitinases. The mechanisms of host chitinase responses may have implications for diagnostic assays as well as novel therapeutic approaches for patients that are at risk of contracting fatal fungal infections.
Citations
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01 Oct 2004
TL;DR: The nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines.
Abstract: Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.
992 citations
TL;DR: A new category of self-growing, fibrous, natural composite materials with controlled physical properties that can be produced in large quantities and over wide areas, based on mycelium, the main body of fungi, is presented.
Abstract: In this work is presented a new category of self-growing, fibrous, natural composite materials with controlled physical properties that can be produced in large quantities and over wide areas, based on mycelium, the main body of fungi. Mycelia from two types of edible, medicinal fungi, Ganoderma lucidum and Pleurotus ostreatus, have been carefully cultivated, being fed by two bio-substrates: cellulose and cellulose/potato-dextrose, the second being easier to digest by mycelium due to presence of simple sugars in its composition. After specific growing times the mycelia have been processed in order to cease their growth. Depending on their feeding substrate, the final fibrous structures showed different relative concentrations in polysaccharides, lipids, proteins and chitin. Such differences are reflected as alterations in morphology and mechanical properties. The materials grown on cellulose contained more chitin and showed higher Young's modulus and lower elongation than those grown on dextrose-containing substrates, indicating that the mycelium materials get stiffer when their feeding substrate is harder to digest. All the developed fibrous materials were hydrophobic with water contact angles higher than 120°. The possibility of tailoring mycelium materials' properties by properly choosing their nutrient substrates paves the way for their use in various scale applications.
276 citations
TL;DR: It is shown that three immune cell receptors– the mannose receptor, NOD2 and TLR9 recognise chitin and act together to mediate an anti-inflammatory response via secretion of the cytokine IL-10, which may prevent inflammation-based damage during fungal infection and restore immune balance after an infection has been cleared.
Abstract: Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease.
214 citations
Cites background from "Chitin, Chitinase Responses, and In..."
...discovery of human chitinases and chitinase-like proteins (CLPs), including some that are constitutively expressed by macrophages and epithelial cells of the lung and digestive tract, suggests the presence of a first line of defence against chitin-containing pathogens, as well as mechanisms for chitin recognition, breakdown and immune-modulation in the human host [9,10]....
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...To date, most immunological studies have mostly used semi-purified commercial sources of chitin derived from shrimp or crab shells [10], making interpretations of the immunological effects of chitin difficult....
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Broad Institute1, Seattle Biomed2, Charité3, Duke University4, University of São Paulo5, University Hospital of Lausanne6, Leibniz Association7, Leeds General Infirmary8, University of Oxford9, Technion – Israel Institute of Technology10, Procter & Gamble11, University of Toronto12, University of Missouri–Kansas City13
TL;DR: These genome analyses identify gene families that are important to the understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response.
Abstract: The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response.
198 citations
Cites background from "Chitin, Chitinase Responses, and In..."
...While studies link chitin identification to an innate or adaptive immune reaction, little is known about how chitin recognition is linked to the immune system (42)....
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...The mammalian immune system has two chitinases and several chi-lectins which identify chitin (42)....
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TL;DR: Different aspects of chitinases and chi-lectins from bacteria, fungi, insects, plants and mammals are discussed.
172 citations
References
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TL;DR: This review focuses on the biology of A. fumigatus, one of the most ubiquitous of the airborne saprophytic fungi, and the diseases it causes, and discusses discussions of genomic and molecular characterization of the organism.
Abstract: Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.
2,083 citations
"Chitin, Chitinase Responses, and In..." refers background or methods in this paper
...However, Candida overgrowth can become symptomatic causing mucosal membrane infections, the most common being thrush and vaginal candidiasis [31–33]....
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...For example, pulmonary fungal infections are typically examined via CT scan, followed up with bronchoalveolar lavage (BAL) and biopsy [27, 30]....
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...In all cases, the most common etiological agents are Candida albicans and Aspergillus fumigatus [27, 29]....
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...Severe systemic Candida infections (Candidemia) and dissemination to internal organs can occur in immunocompromised patients [31– 33]....
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...Moreover, the galactomannan assay is not useful for other fungal pathogens, including Candida [30, 37]. β-1,3-glucan serological detection assays are more widely used today because they can detect a wide range of fungi, including Aspergillus and Candida, but they do not detect zygo- or mucormycosis or cryptococcal disease [38]....
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01 Jan 2009
TL;DR: A review of the biology of Aspergillus fumigatus and the diseases it causes can be found in this article, where the authors discuss genomic and molecular characterization of the organism, clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunOCompromised hosts, identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and problems associated with antifungal therapy.
Abstract: SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.
2,040 citations
TL;DR: Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi.
Abstract: Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.
1,528 citations
TL;DR: Understanding the molecular mechanisms behind Dectin-1 functions has revealed new concepts, including collaborative signalling with the Toll-like receptors (TLRs) and the use of spleen tyrosine kinase (SYK), that have implications for the role of other non-TLR pattern-recognition receptors in immunity.
Abstract: Dectin-1 is a natural killer (NK)-cell-receptor-like C-type lectin that is thought to be involved in innate immune responses to fungal pathogens. This transmembrane signalling receptor mediates various cellular functions, from fungal binding, uptake and killing, to inducing the production of cytokines and chemokines. These activities could influence the resultant immune response and can, in certain circumstances, lead to autoimmunity and disease. As I discuss here, understanding the molecular mechanisms behind these functions has revealed new concepts, including collaborative signalling with the Toll-like receptors (TLRs) and the use of spleen tyrosine kinase (SYK), that have implications for the role of other non-TLR pattern-recognition receptors in immunity.
1,042 citations
"Chitin, Chitinase Responses, and In..." refers background in this paper
...The recognition of fungal cellular features, in particular fungal cell wall components, by the immune system of the host is an important element for mounting an antifungal defense response [3, 5, 26, 43]....
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TL;DR: It is shown that deficiency of dectin-1, the myeloid receptor for β-glucan, rendered mice susceptible to infection with Candida albicans, and a signaling non–Toll-like pattern-recognition receptor required for the induction of protective immune responses is established.
Abstract: Beta-Glucan is one of the most abundant polysaccharides in fungal pathogens, yet its importance in antifungal immunity is unclear. Here we show that deficiency of dectin-1, the myeloid receptor for -glucan, rendered mice susceptible to infection with Candida albicans. Dectin-1-deficient leukocytes demonstrated significantly impaired responses to fungi even in the presence of opsonins. Impaired leukocyte responses were manifested in vivo by reduced inflammatory cell recruitment after fungal infection, resulting in substantially increased fungal burdens and enhanced fungal dissemination. Our results establish a fundamental function for Beta-glucan recognition by dectin-1 in antifungal immunity and demonstrate a signaling non–Toll-like pattern-recognition receptor required for the induction of protective immune responses.
1,031 citations
"Chitin, Chitinase Responses, and In..." refers background in this paper
...Complement-coated β-glucan is recognized by complement receptor-3 [55, 56]....
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...Dectin-1 recognition of β-glucans results in an MYD88-dependent pathway activation [3, 5, 44, 55, 57]....
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...Fc gamma receptor (FcγR) may signal through dectin-2 when activated by N-linked mannan [3, 45, 47, 55]....
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