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      Characterisation of cuticular inflation development and ultrastructure in Trichuris muris using correlative X-ray computed tomography and electron microscopy

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          Abstract

          The parasitic nematode Trichuris trichiura is a significant burden on public health in developing countries, and currently available drugs exhibit a poor cure rate. Worms live within a specialised tunnel of host intestinal epithelial cells and have anterior-ventral projections of the cuticle termed “cuticular inflations”, which are thought to be involved in host-parasite interactions. This work aimed to characterise structure and suggest a function of cuticular inflations in the most tractable and widely-used model of trichuriasis, Trichuris muris. Using scanning electron microscopy, we show for the first time that most cuticular inflations develop between the second and third larval moults. Correlative X-ray computed tomography (CT)-steered Serial Block Face Scanning Electron Microscopy (SBF-SEM) and transmission electron microscopy enabled ultrastructural imaging of cuticular inflations, and showed the presence of an additional, web-like layer of cuticle between the median and cortical layers of the inflation. Additionally, we characterised variation in inflation morphology, resolving debate as to the inflations’ true shape in situ. Cells underlying the inflations had many mitochondria, and we highlight their potential capacity for active transport as an area for future investigation. Overall, insights from the powerful imaging techniques used provide an excellent basis for future study of cuticular inflation function.

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          Most cited references24

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          Enhancing Serial Block-Face Scanning Electron Microscopy to Enable High Resolution 3-D Nanohistology of Cells and Tissues

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            Trichuris muris: a model of gastrointestinal parasite infection

            Infection with soil-transmitted gastrointestinal parasites, such as Trichuris trichiura, affects more than a billion people worldwide, causing significant morbidity and health problems especially in poverty-stricken developing countries. Despite extensive research, the role of the immune system in triggering parasite expulsion is incompletely understood which hinders the development of anti-parasite therapies. Trichuris muris infection in mice serves as a useful model of T. trichiura infection in humans and has proven to be an invaluable tool in increasing our understanding of the role of the immune system in promoting either susceptibility or resistance to infection. The old paradigm of a susceptibility-associated Th1 versus a resistance-associated Th2-type response has been supplemented in recent years with cell populations such as novel innate lymphoid cells, basophils, dendritic cells and regulatory T cells proposed to play an active role in responses to T. muris infection. Moreover, new immune-controlled mechanisms of expulsion, such as increased epithelial cell turnover and mucin secretion, have been described in recent years increasing the number of possible targets for anti-parasite therapies. In this review, we give a comprehensive overview of experimental work conducted on the T. muris infection model, focusing on important findings and the most recent reports on the role of the immune system in parasite expulsion.
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              Acquired immunity to Trichuris muris in the albino laboratory mouse.

              D Wakelin (1967)
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                Author and article information

                Contributors
                jxo512@med.miami.edu
                Kathryn.else@manchester.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 April 2020
                3 April 2020
                2020
                : 10
                : 5846
                Affiliations
                [1 ]ISNI 0000000121662407, GRID grid.5379.8, Henry Royce Institute, Department of Materials, The University of Manchester, Oxford Road, ; Manchester, M13 9PL United Kingdom
                [2 ]ISNI 0000000121662407, GRID grid.5379.8, The Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Oxford Road, ; Manchester, M13 9PL United Kingdom
                [3 ]ISNI 0000 0004 0450 1654, GRID grid.449998.1, Wellcome Centre for Cell Matrix Research, The University of Manchester, Oxford Road, ; Manchester, M13 9PL United Kingdom
                Article
                61916
                10.1038/s41598-020-61916-0
                7125116
                32246000
                1f37ef40-c817-401d-ae4f-2ea817d32d1b
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 January 2020
                : 26 February 2020
                Funding
                Funded by: Carl Zeiss AG
                Award ID: PhD Studentship
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 203128/Z/16/Z
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000266, Engineering and Physical Sciences Research Council;
                Award ID: EP/F007906/1
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: 695638 CORREL-CT
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                microbiology,parasitology,imaging techniques
                Uncategorized
                microbiology, parasitology, imaging techniques

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