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      Extracellular Vesicle-Mediated Communication Within Host-Parasite Interactions

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          Abstract

          Extracellular vesicles (EVs) are small membrane-surrounded structures released by different kinds of cells (normal, diseased, and transformed cells) in vivo and in vitro that contain large amounts of important substances (such as lipids, proteins, metabolites, DNA, RNA, and non-coding RNA (ncRNA), including miRNA, lncRNA, tRNA, rRNA, snoRNA, and scaRNA) in an evolutionarily conserved manner. EVs, including exosomes, play a role in the transmission of information, and substances between cells that is increasingly being recognized as important. In some infectious diseases such as parasitic diseases, EVs have emerged as a ubiquitous mechanism for mediating communication during host-parasite interactions. EVs can enable multiple modes to transfer virulence factors and effector molecules from parasites to hosts, thereby regulating host gene expression, and immune responses and, consequently, mediating the pathogenic process, which has made us rethink our understanding of the host-parasite interface. Thus, here, we review the present findings regarding EVs (especially exosomes) and recognize the role of EVs in host-parasite interactions. We hope that a better understanding of the mechanisms of parasite-derived EVs may provide new insights for further diagnostic biomarker, vaccine, and therapeutic development.

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          Most cited references104

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          Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.

          Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells.
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            Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.

            Dendritic cells constitutively secrete a population of small (50-90 nm diameter) Ag-presenting vesicles called exosomes. When sensitized with tumor antigenic peptides, dendritic cells produce exosomes, which stimulate anti-tumor immune responses and the rejection of established tumors in mice. Using a systematic proteomic approach, we establish the first extensive protein map of a particular exosome population; 21 new exosomal proteins were thus identified. Most proteins present in exosomes are related to endocytic compartments. New exosomal residents include cytosolic proteins most likely involved in exosome biogenesis and function, mainly cytoskeleton-related (cofilin, profilin I, and elongation factor 1alpha) and intracellular membrane transport and signaling factors (such as several annexins, rab 7 and 11, rap1B, and syntenin). Importantly, we also identified a novel category of exosomal proteins related to apoptosis: thioredoxin peroxidase II, Alix, 14-3-3, and galectin-3. These findings led us to analyze possible structural relationships between exosomes and microvesicles released by apoptotic cells. We show that although they both represent secreted populations of membrane vesicles relevant to immune responses, exosomes and apoptotic vesicles are biochemically and morphologically distinct. Therefore, in addition to cytokines, dendritic cells produce a specific population of membrane vesicles, exosomes, with unique molecular composition and strong immunostimulating properties.
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              Astrocytes and Glioblastoma cells release exosomes carrying mtDNA.

              Cells can exchange information not only by means of chemical and/or electrical signals, but also via microvesicles released into the intercellular space. The present paper, for the first time, provides evidence that Glioblastoma and Astrocyte cells release microvesicles, which carry mitochondrial DNA (mtDNA). These microvesicles have been characterised as exosomes in view of the presence of some protein markers of exosomes, such as Tsg101, CD9 and Alix. Thus, the important finding has been obtained that bonafide exosomes, constitutively released by Glioblastoma cells and Astrocytes, can carry mtDNA, which can be, therefore, transferred between cells. This datum may help the understanding of some diseases due to mitochondrial alterations.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                15 January 2019
                2018
                : 9
                : 3066
                Affiliations
                [1] 1Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China
                [2] 2Key Laboratory of Tropical Disease Control (SYSU), Ministry of Education , Guangzhou, China
                [3] 3Provincial Engineering Technology Research Center for Biological Vector Control , Guangzhou, China
                Author notes

                Edited by: Wanderley De Souza, Universidade Federal do Rio de Janeiro, Brazil

                Reviewed by: Eden Ramalho Ferreira, Federal University of São Paulo, Brazil; Emile Santos Barrias, Instituto Nacional de Metrologia, Qualidade e Tecnologia, Brazil

                *Correspondence: Xi Sun sunxi2@ 123456mail.sysu.edu.cn

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work and co-first authorship

                Article
                10.3389/fimmu.2018.03066
                6340962
                30697211
                9291b5d4-36c9-45a9-b4cf-556d2fc4d0ad
                Copyright © 2019 Wu, Wang, Li, Wang, Wu and Sun.

                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) and the copyright owner(s) 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
                : 30 August 2018
                : 11 December 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 145, Pages: 16, Words: 13036
                Categories
                Immunology
                Review

                Immunology
                parasite,extracellular vesicle,intercellular communication,parasite-host interaction,exosome

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