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      Recombinant Toxoplasma gondii phosphoglycerate mutase 2 confers protective immunity against toxoplasmosis in BALB/c mice Translated title: La phosphoglycérate mutase 2 recombinante de Toxoplasma gondii confère une immunité protectrice contre la toxoplasmose chez les souris BALB/c

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          Abstract

          Toxoplasmosis is one of the most widespread zoonoses worldwide. It has a high incidence and can result in severe disease in humans and livestock. Effective vaccines are needed to limit and prevent infection with Toxoplasma gondii. In this study, we evaluated the immuno-protective efficacy of a recombinant Toxoplasma gondii phosphoglycerate mutase 2 (rTgPGAM 2) against T. gondii infection in BALB/c mice. We report that the mice nasally immunised with rTgPGAM 2 displayed significantly higher levels of special IgG antibodies against rTgPGAM 2 (including IgG1, IgG2a and IgAs) and cytokines (including IFN-γ, IL-2 and IL-4) in their blood sera and supernatant of cultured spleen cells compared to those of control animals. In addition, an increased number of spleen lymphocytes and enhanced lymphocyte proliferative responses were observed in the rTgPGAM 2-immunised mice. After chronic infection and lethal challenge with the highly virulent T. gondii RH strain by oral gavage, the survival time of the rTgPGAM 2-immunised mice was longer ( P < 0.01) and the survival rate (70%) was higher compared with the control mice ( P < 0.01). The reduction rate of brain and liver tachyzoites in rTgPGAM 2-vaccinated mice reached approximately 57% and 69% compared with those of the control mice ( P < 0.01). These results suggest that rTgPGAM 2 can generate protective immunity against T. gondii infection in BALB/c mice and may be a promising antigen in the further development of an effective vaccine against T. gondii infection.

          Translated abstract

          La toxoplasmose est une des zoonoses les plus répandues dans le monde entier. Elle a une forte incidence et entraîne des dommages graves pour les humains et le bétail. Des vaccins efficaces sont nécessaires pour limiter et empêcher l’infection par Toxoplasma gondii. Dans cette étude, nous avons évalué l’efficacité immunitaire protectrice d’une phosphoglycérate mutase 2 recombinante de T. gondii (rTgPGAM 2) contre l’infection par T. gondii chez les souris BALB/c. Nous rapportons que les souris immunisées par voie nasale avec rTgPGAM 2 montraient des niveaux significativement plus élevés d’anticorps IgG spécifiques contre rTgPGAM 2 (y compris IgG1, IgG2a et IgA) et de cytokines (y compris IFN-γ, IL-2 et IL-4), dans leur sérum sanguin et dans le surnageant de cellules de rate en culture, par rapport à ceux des animaux témoins. En outre, un nombre accru de lymphocytes dans la rate et des réponses prolifératives lymphocytaires améliorées ont été observées chez les souris immunisées par rTgPGAM 2. Après l’infection chronique et une provocation létale avec la souche de T. gondii RH, très virulente, par gavage oral, le temps de survie des souris rTgPGAM 2 immunisées était plus long ( P < 0.01) et le taux de survie (70 %) était plus élevé que chez les souris témoins ( P < 0.01). Le taux de réduction des tachyzoïtes du cerveau et du foie chez les souris vaccinées par rTgPGAM 2 a atteint environ 57 % et 69 % par rapport à ceux des souris témoins ( P < 0.01). Ces résultats suggèrent que rTgPGAM 2 peut générer une immunité protectrice contre une infection par T. gondii chez les souris BALB/c et peut être un antigène prometteur dans la poursuite du développement d’un vaccin efficace contre l’infection par T. gondii.

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          Most cited references 43

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          Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts.

           J Dubey,  D S Lindsay,  C Speer (1998)
          Infections by the protozoan parasite Toxoplasma gondii are widely prevalent world-wide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial stages of T. gondii; and the mode of penetration of T. gondii. The review provides a detailed account of the biology of tissue cysts and bradyzoites including in vivo and in vitro development, methods of separation from host tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro stage conversion from sporozoites to tachyzoites to bradyzoites and from bradyzoites to tachyzoites to bradyzoites is also discussed.
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            Immune response and immunopathology during toxoplasmosis.

            Toxoplasma gondii is a protozoan parasite of medical and veterinary significance that is able to infect any warm-blooded vertebrate host. In addition to its importance to public health, several inherent features of the biology of T. gondii have made it an important model organism to study host-pathogen interactions. One factor is the genetic tractability of the parasite, which allows studies on the microbial factors that affect virulence and allows the development of tools that facilitate immune studies. Additionally, mice are natural hosts for T. gondii, and the availability of numerous reagents to study the murine immune system makes this an ideal experimental system to understand the functions of cytokines and effector mechanisms involved in immunity to intracellular microorganisms. In this article, we will review current knowledge of the innate and adaptive immune responses required for resistance to toxoplasmosis, the events that lead to the development of immunopathology, and the natural regulatory mechanisms that limit excessive inflammation during this infection.
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              Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells.

              Cells infected with the intracellular protozoan parasite Toxoplasma gondii undergo up-regulation of pro-inflammatory cytokines, organelle redistribution, and protection from apoptosis. To examine the molecular basis of these and other changes, gene expression profiles of human foreskin fibroblasts infected with Toxoplasma were studied using human cDNA microarrays consisting of approximately 22,000 known genes and uncharacterized expressed sequence tags. Early during infection (1-2 h), <1% of all genes show a significant change in the abundance of their transcripts. Of the 63 known genes in this group, 27 encode proteins associated with the immune response. These genes are also up-regulated by secreted, soluble factors from extracellular parasites indicating that the early response does not require parasite invasion. Later during infection, genes involved in numerous host cell processes, including glucose and mevalonate metabolism, are modulated. Many of these late genes are dependent on the direct presence of the parasite; i.e. secreted products from either the parasite or infected cells are insufficient to induce these changes. These results reveal several previously unknown effects on the host cell and lay the foundation for detailed analysis of their role in the host-pathogen interaction.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2016
                16 March 2016
                : 23
                : ( publisher-idID: parasite/2016/01 )
                Affiliations
                [1 ] Academy of Basic Medicine, Shanxi Medical University Taiyuan Shanxi 030001 PR China
                [2 ] Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan Shanxi 030001 PR China
                [3 ] Department of General Surgery, Xi’an Red Cross Hospital Xi’an Shanxi 710000 PR China
                [4 ] Department of Infection Control, The Central Hospital of Enshi Prefecture Enshi Hubei 445000 PR China
                [5 ] Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland Private bag 92-019 Auckland 1142 New Zealand
                [6 ] Laboratory Animal Center, Shanxi Medical University; Shanxi Key Laboratory of Laboratory Animals and Animal Models of Human Diseases Taiyuan Shanxi 030001 PR China
                Author notes
                Article
                parasite150077 10.1051/parasite/2016012
                10.1051/parasite/2016012
                4794628
                26984115
                © H.-L. Wang et al., published by EDP Sciences, 2016

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 53, Pages: 10
                Categories
                Research Article

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