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      Bacterial ghosts as adjuvants: mechanisms and potential

      review-article
      1 , 2 , 1 , 1 ,
      Veterinary Research
      BioMed Central

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          Abstract

          Bacterial ghosts (BG) are empty cell envelopes derived from Gram-negative bacteria. They contain many innate immunostimulatory agonists, and are potent activators of a broad range of cell types involved in innate and adaptive immunity. Several considerable studies have demonstrated the effectiveness of BG as adjuvants as well as their ability to induce proinflammatory cytokine production by a range of immune and non-immune cell types. These proinflammatory cytokines trigger a generalized recruitment of T and B lymphocytes to lymph nodes that maximize the chances of encounter with their cognate antigen, and subsequent elicitation of potent immune responses. The plasticity of BG has allowed for the generation of envelope-bound foreign antigens in immunologically active forms that have proven to be effective vaccines in animal models. Besides their adjuvant property, BG also effectively deliver DNA-encoded antigens to dendritic cells, thereby leading to high transfection efficiencies, which subsequently result in higher gene expressions and improved immunogenicity of DNA-based vaccines. In this review, we summarize our understanding of BG interactions with the host immune system, their exploitation as an adjuvant and a delivery system, and address important areas of future research interest.

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          Most cited references99

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          The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large groups of microorganisms. Recognition of these patterns allows the innate immune system not only to detect the presence of an infectious microbe, but also to determine the type of the infecting pathogen. Pattern recognition receptors activate conserved host defense signaling pathways that control the expression of a variety of immune response genes.
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            Cell biology of antigen processing in vitro and in vivo.

            The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
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              Recognition of pathogen-associated molecular patterns by TLR family.

              Toll-like receptors (TLRs) are type I transmembrane proteins involved in innate immunity by recognizing microbial conserved structures. Recent studies have shown that TLR3 recognizes dsRNA, a viral product, whereas TLR9 recognizes unmethylated CpG motifs frequently found in the genome of bacteria and viruses, but not vertebrates. TLR7 recognizes small synthetic immune modifiers including imiquimod, R-848, loxoribine, and bropirimine, all of which are already applied or promising for clinical use against viral infections and cancers. Plasmacytoid dendritic cells express TLR7 and TLR9, and respond to TLR7 and TLR9 ligands by producing a large amount of interferon (IFN-alpha). These results indicate that TLR3, TLR7 and TLR9 may play an important role in detecting and combating viral infections.

                Author and article information

                Contributors
                aalirshad@gmail.com
                dar.pervaiz@gmail.com
                gayeonwon@gmail.com
                johnhlee@jbnu.ac.kr
                Journal
                Vet Res
                Vet. Res
                Veterinary Research
                BioMed Central (London )
                0928-4249
                1297-9716
                24 June 2017
                24 June 2017
                2017
                : 48
                : 37
                Affiliations
                [1 ]ISNI 0000 0004 0470 4320, GRID grid.411545.0, College of Veterinary Medicine, , Chonbuk National University, ; Iksan, 54596 Republic of Korea
                [2 ]ISNI 0000 0001 2184 944X, GRID grid.267337.4, Department of Medicine, College of Medicine and Life Sciences, , University of Toledo, ; Toledo, OH 43614 USA
                Article
                442
                10.1186/s13567-017-0442-5
                5482964
                28645300
                22627537-bfb8-487d-8dc2-5adf4b24ce7e
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 October 2016
                : 4 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2015R1A2A1A14001011
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Veterinary medicine
                Veterinary medicine

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