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      Using lymph node transplantation as an approach to image cellular interactions between the skin and draining lymph nodes during parasitic infections ☆☆

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          Abstract

          The growing use of protozoan parasites expressing fluorescent reporter genes, together with advances in microscopy, is enabling visualisation of their behaviour and functions within the host from the very earliest stages of infection with previously unparalleled spatiotemporal resolution. These developments have begun to provide novel insights, which are informing our understanding of where host immune responses may be initiated, which cells are involved and the types of response that are elicited. Here we will review some of these recent observations that highlight the importance of cellular communication between the site of infection and the draining lymph node (dLN) in establishing infection and immunity. We also highlight a number of remaining challenges and unknowns that arise through our inability to follow and fate map the journey of a single cell between spatially separated tissue sites. In response to these challenges, we review a recently described experimental strategy that extends the spatial and temporal limits of previous imaging approaches, most significantly allowing longitudinal analysis of cellular migration between the skin and draining lymph nodes in vivo, without the requirement for invasive surgery.

          Graphical abstract

          Highlights

          • Role of skin and LN communication in establishing infection and immunity

          • A technique to extend the spatial and temporal limits of tissue imaging

          • This approach does not require invasive surgery for imaging.

          • We can follow the journey of a single cell between spatially separated tissue sites.

          • We outline future applications for this approach.

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          Most cited references37

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          Quantitative imaging of Plasmodium transmission from mosquito to mammal.

          Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into the dermis and must reach the liver before infecting erythrocytes and causing disease. We present here a quantitative, real-time analysis of the fate of parasites transmitted in a rodent system. We show that only a proportion of the parasites enter blood capillaries, whereas others are drained by lymphatics. Lymph sporozoites stop at the proximal lymph node, where most are degraded inside dendritic leucocytes, but some can partially differentiate into exoerythrocytic stages. This previously unrecognized step of the parasite life cycle could influence the immune response of the host, and may have implications for vaccination strategies against the preerythrocytic stages of the parasite.
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            Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity.

            Peptide:MHC II complexes derived from a fluorescent antigen were detected in vivo to identify the cells that present subcutaneously injected antigen to CD4 T cells. Skin-derived dendritic cells (DCs) that acquired the antigen while in the draining lymph nodes were the first cells to display peptide:MHC II complexes. Presentation by these cells induced CD69, IL-2 production, and maximal proliferation by the T cells. Later, DCs displaying peptide:MHC II complexes migrated from the injection site via a G protein-dependent mechanism. Presentation by these migrants sustained expression of the IL-2 receptor and promoted delayed type hypersensitivity. Therefore, presentation of peptide:MHC II complexes derived from a subcutaneous antigen occurs in two temporally distinct waves with different functional consequences.
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              Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes.

              Previous studies have shown that mosquitoes inject Plasmodium sporozoites into avascular portions of the skin of their rodent host rather than directly into the blood circulation. Then, over time, these sporozoites move into the circulation, from where they reach the liver to initiate a malaria infection. By use of intravital microscopy of the skin, we present direct morphological evidence of mosquito probing that introduces sporozoites into avascular tissue, of the migration of these sporozoites through the dermis and into blood vessels, and of the role of anti-sporozoite antibodies in blocking sporozoite invasion of these dermal blood vessels.
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                Author and article information

                Journal
                Parasitol Int
                Parasitol. Int
                Parasitology International
                Elsevier
                1383-5769
                1873-0329
                1 February 2014
                February 2014
                : 63
                : 1
                : 165-170
                Affiliations
                Wellcome Trust Centre For Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, G12 8TA, United Kingdom
                Author notes
                [* ]Corresponding author. Tel.: + 44 141 330 8417; fax: + 44 141 330 4297. james.brewer@ 123456glasgow.ac.uk
                [1]

                Joint first authors.

                Article
                S1383-5769(13)00111-6
                10.1016/j.parint.2013.07.010
                3863950
                23892176
                8bd63963-80f8-4e53-9a6a-d647091e66f1
                © 2013 The Authors

                This document may be redistributed and reused, subject to certain conditions.

                History
                Categories
                Review

                Parasitology
                infection,in vivo imaging,immunology,microscopy
                Parasitology
                infection, in vivo imaging, immunology, microscopy

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