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      Extracellular Vesicle-Associated Transitory Cell Wall Components and Their Impact on the Interaction of Fungi with Host Cells

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          Abstract

          Classic cell wall components of fungi comprise the polysaccharides glucans and chitin, in association with glycoproteins and pigments. During the last decade, however, system biology approaches clearly demonstrated that the composition of fungal cell walls include atypical molecules historically associated with intracellular or membrane locations. Elucidation of mechanisms by which many fungal molecules are exported to the extracellular space suggested that these atypical components are transitorily located to the cell wall. The presence of extracellular vesicles (EVs) at the fungal cell wall and in culture supernatants of distinct pathogenic species suggested a highly functional mechanism of molecular export in these organisms. Thus, the passage of EVs through fungal cell walls suggests remarkable molecular diversity and, consequently, a potentially variable influence on the host antifungal response. On the basis of information derived from the proteomic characterization of fungal EVs from the yeasts Cryptoccocus neoformans and Candida albicans and the dimorphic fungi Histoplasma capsulatum and Paracoccidioides brasiliensis, our manuscript is focused on the clear view that the fungal cell wall is much more complex than previously thought.

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          Most cited references111

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          Immune recognition. A new receptor for beta-glucans.

          The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.
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            Activation of the innate immune receptor Dectin-1 upon formation of a “phagocytic synapse”

            Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 is a pattern recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular anti-microbial activity, including phagocytosis and production of reactive oxygen species 1, 2 . In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 are excluded (Supplementary Figure 1). The “phagocytic synapse” now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular anti-microbial responses only when they are required.
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              Interactions of fungal pathogens with phagocytes.

              The surveillance and elimination of fungal pathogens rely heavily on the sentinel behaviour of phagocytic cells of the innate immune system, especially macrophages and neutrophils. The efficiency by which these cells recognize, uptake and kill fungal pathogens depends on the size, shape and composition of the fungal cells and the success or failure of various fungal mechanisms of immune evasion. In this Review, we describe how fungi, particularly Candida albicans, interact with phagocytic cells and discuss the many factors that contribute to fungal immune evasion and prevent host elimination of these pathogenic microorganisms.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                08 July 2016
                2016
                : 7
                : 1034
                Affiliations
                [1] 1Laboratório de Glicobiologia de Eucariotos, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro Brazil
                [2] 2Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY USA
                [3] 3Veterans Administration Medical Center, Northport, NY USA
                [4] 4Department of Microbiology and Immunology and Medicine, Albert Einstein College of Medicine, Bronx, NY USA
                [5] 5Fundação Oswaldo Cruz, Centro de Desenvolvimento Tecnológico em Saúde, Rio de Janeiro Brazil
                Author notes

                Edited by: Agostinho Carvalho, University of Minho, Portugal

                Reviewed by: Olaf Kniemeyer, Hans-Knoell-Institute, Germany; Sophie Lev, University of Sydney at Westmead Hospital, Australia

                *Correspondence: Leonardo Nimrichter, nimrichter@ 123456micro.ufrj.br Marcio L. Rodrigues, marciolr@ 123456cdts.fiocruz.br

                This article was submitted to Fungi and Their Interactions, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.01034
                4937017
                27458437
                d4f6d4e1-0359-4abb-96d9-75f165e81e02
                Copyright © 2016 Nimrichter, de Souza, Del Poeta, Nosanchuk, Joffe, Tavares and Rodrigues.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 April 2016
                : 20 June 2016
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 118, Pages: 11, Words: 0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                fungal cell wall,extracellular vesicles,proteomics,host cell,cell wall remodeling

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