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      A temperature sensitive Mycobacterium paragordonae induces enhanced protective immune responses against mycobacterial infections in the mouse model

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      Scientific Reports
      Nature Publishing Group UK

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          Abstract

          Recently, we introduced a temperature sensitive Mycobacterium spp ., Mycobacterium paragordonae (Mpg). Here, we checked its potential as a candidate for live vaccination against Mycobacterium tuberculosis and Mycobacterium abscessus. Intravenous infections of mice with Mpg led to lower colony forming units (CFUs) compared to infection with BCG, suggesting its usefulness as a live vaccine. The analyses of immune responses indicated that the highly protective immunity elicited by Mpg was dependent on effective dendritic maturation, shift of cytokine patterns and antibody production toward a Th1 phenotype, and enhanced cytotoxic T cell response. Compared to BCG, Mpg showed a more effective protective immune response in the vaccinated mice against challenges with 2 different mycobacterial strains, M. tuberculosis H37Ra or M. abscessus Asan 50594. Our data suggest that a temperature sensitive Mpg may be a potentially powerful candidate vaccine strain to induce enhanced protective immune responses against M. tuberculosis and M. abscessus.

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          CCR7 and its ligands: balancing immunity and tolerance.

          A key feature of the immune system is its ability to induce protective immunity against pathogens while maintaining tolerance towards self and innocuous environmental antigens. Recent evidence suggests that by guiding cells to and within lymphoid organs, CC-chemokine receptor 7 (CCR7) essentially contributes to both immunity and tolerance. This receptor is involved in organizing thymic architecture and function, lymph-node homing of naive and regulatory T cells via high endothelial venules, as well as steady state and inflammation-induced lymph-node-bound migration of dendritic cells via afferent lymphatics. Here, we focus on the cellular and molecular mechanisms that enable CCR7 and its two ligands, CCL19 and CCL21, to balance immunity and tolerance.
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            The success and failure of BCG - implications for a novel tuberculosis vaccine.

            Over the past 50 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has maintained its position as the world's most widely used vaccine, despite showing highly variable efficacy (0-80%) in different trials. The efficacy of BCG in adults is particularly poor in tropical and subtropical regions. Studies in animal models of TB, supported by data from clinical BCG trials in humans, indicate that this failure is related to pre-existing immune responses to antigens that are common to environmental mycobacteria and Mycobacterium tuberculosis. Here, we discuss the potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy.
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              Mycobacterium abscessus Complex Infections in Humans

              New treatments, rapid and inexpensive identification methods, and measures to contain nosocomial transmission and outbreaks are urgently needed.
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                Author and article information

                Contributors
                kbumjoon@snu.ac.kr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 November 2017
                9 November 2017
                2017
                : 7
                : 15230
                Affiliations
                ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, ; Seoul, Korea
                Article
                15458
                10.1038/s41598-017-15458-7
                5680210
                29123166
                6b0dfbb4-179d-4758-8b4b-6ae35dd6a8be
                © The Author(s) 2017

                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
                : 9 May 2017
                : 25 October 2017
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