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      Evaluation of immune protection against Toxoplasma gondii infection in mice induced by a multi-antigenic DNA vaccine containing TgGRA24, TgGRA25 and TgMIC6 Translated title: Évaluation de la protection immunitaire contre l’infection par Toxoplasma gondii chez la souris, induite par un vaccin à ADN multi-antigénique contenant TgGRA24, TgGRA25 et TgMIC6

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          Abstract

          Toxoplasma gondii infection is prevalent in humans and animals worldwide. In this study, recombinant eukaryotic expression plasmids (pVAX-GRA24, pVAX-GRA25 and pVAX-MIC6) were constructed, and then injected into Kunming mice intramuscularly, as cocktailed plasmids or as single-gene plasmids. We evaluated immune protective responses by detecting the titer of antibodies and cytokine production of IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-23, the percentages of the subclasses of T lymphocytes, as well as the records of the survival time and cyst decrement in the brain of the mouse model after challenge with the T. gondii RH and Pru strains, respectively. Compared with the control groups, antibody and cytokine production were significantly increased, while the survival times of mice in all immunized groups were also prolonged, and the number of T. gondii cysts in their brains were decreased significantly (29.03% for pVAX-GRA24; 40.88% for pVAX-GRA25; 37.70% for pVAX-MIC6; 48.06% for pVAX-GRA24 + pVAX-GRA25; and 55.37% for pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). The mouse group immunized with the three-gene cocktail (TgGRA24 + TgGRA25 + TgMIC6) had better performance in each detection index than the mouse groups immunized with the two-gene cocktail of TgGRA24 + TgGRA25, which was better than that in the group immunized with the single gene vaccine of TgGRA24, TgMIC6 or TgGRA25. In conclusion, TgGRA24 or TgGRA25 may be good vaccine candidates against T. gondii infection, but the three-gene cocktail of TgGRA24, TgMIC6 and TgGRA25 may induce the strongest protective immunity. Further studies of multi-antigenic DNA vaccines or cocktailed vaccines against T. gondii infection are necessary.

          Translated abstract

          L’infection à Toxoplasma gondii est répandue chez les humains et les animaux dans le monde entier. Dans cette étude, des plasmides d’expression eucaryotes recombinants (pVAX-GRA24, pVAX-GRA25 et pVAX-MIC6) ont été construits, puis injectés à des souris Kunming par voie intramusculaire, comme cocktails de plasmides ou comme plasmides à un seul gène. Nous avons évalué les réponses de protection immunitaire en détectant le titre des anticorps et la production de cytokines IFN-γ, IL-2, IL-4, IL-10, IL-12 et IL-23, les pourcentages des sous-classes des lymphocytes T, ainsi qu’en mesurant les temps de survie et de décrément des kystes dans le cerveau du modèle souris après challenge par les souches RH et Pru de T. gondii, respectivement. Comparativement aux groupes témoins, la production d’anticorps et de cytokines était significativement accrue, tandis que le temps de survie des souris de tous les groupes immunisés était également prolongé et que le nombre de kystes de T. gondii dans leur cerveau diminuait de manière significative (29,03 % pour pVAX-GRA24 ; 40,88 % pour pVAX-GRA25 ; 37,70 % pour pVAX-MIC6 ; 48,06 % pour pVAX-GRA24 + pVAX-GRA25 ; 55,37 % pour pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). Le groupe de souris immunisées avec les cocktails à trois gènes (TgGRA24 + TgGRA25 + TgMIC6) présentait la meilleure performance dans chaque indice de détection par rapport aux groupes de souris immunisées avec des cocktails à deux gènes de TgGRA24 + TgGRA25, qui était supérieur à ceux immunisés avec les vaccins monogéniques TgGRA24, TgMIC6 ou TgGRA25. En conclusion, TgGRA24 ou TgGRA25 peuvent être de bons candidats au vaccin contre l’infection à T. gondii, mais un cocktail à trois gènes de TgGRA24, TgMIC6 et TgGRA25 peut induire la plus forte immunité protectrice. Des études supplémentaires sur les vaccins à ADN multi-antigéniques ou les vaccins en cocktail contre l’infection à T. gondii sont nécessaires.

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          Most cited references 34

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          Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

          Chemokines play a central role in regulating processes essential to the immune function of T cells 1-3 , such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen T. gondii in the brains of chronically infected mice. This chemokine boosts T cell function in two different ways: it maintains the effector T cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Remarkably, these statistics are not Brownian; rather, CD8+ T cell motility in the brain is well described by a generalized Lévy walk. According to our model, this surprising feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T cell behavior is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys 4-10 , and CXCL10 aids T cells in shortening the average time to find rare targets.
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            The history of Toxoplasma gondii--the first 100 years.

            In this paper the history of Toxoplasma gondii and toxoplasmosis is reviewed. This protozoan parasite was first discovered in 1908 and named a year later. Its medical importance remained unknown until 1939 when T. gondii was identified in tissues of a congenitally infected infant, and veterinary importance became known when it was found to cause abortion storms in sheep in 1957. The discovery of a T. gondii specific antibody test, Sabin-Feldman dye test in 1948 led to the recognition that T. gondii is a common parasite of warm-blooded hosts with a worldwide distribution. Its life cycle was not discovered until 1970 when it was found that felids are its definitive host and an environmentally resistant stage (oocyst) is excreted in feces of infected cats. The recent discovery of its common infection in certain marine wildlife (sea otters) indicates contamination of our seas with T. gondii oocysts washed from land. Hygiene remains the best preventive measure because currently there is no vaccine to prevent toxoplasmosis in humans.
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              Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response.

              Apicomplexan parasites exhibit actin-dependent gliding motility that is essential for migration across biological barriers and host cell invasion. Profilins are key contributors to actin polymerization, and the parasite Toxoplasma gondii possesses a profilin-like protein that is recognized by Toll-like receptor TLR11 in the host innate immune system. Here, we show by conditional disruption of the corresponding gene that T.gondii profilin, while not required for intracellular growth, is indispensable for gliding motility, host cell invasion, active egress from host cells, and virulence in mice. Furthermore, parasites lacking profilin are unable to induce TLR11-dependent production in vitro and in vivo of the defensive host cytokine interleukin-12. Thus, profilin is an essential element of two aspects of T. gondii infection. Like bacterial flagellin, profilin plays a role in motility while serving as a microbial ligand recognized by the host innate immune system.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2019
                19 September 2019
                : 26
                : ( publisher-idID: parasite/2019/01 )
                Affiliations
                [1 ] State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences Lanzhou Gansu Province 730046 PR China
                [2 ] College of Animal Science and Technology, Anhui Agricultural University Hefei Anhui Province 230036 PR China
                [3 ] Ningbo University School of Medicine Ningbo Zhejiang Province 315211 PR China
                Author notes
                [* ]Corresponding author: chenjia@ 123456nbu.edu.cn
                Article
                parasite190055 10.1051/parasite/2019050
                10.1051/parasite/2019050
                6752116
                31535970
                © X-P. Xu et al., published by EDP Sciences, 2019

                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: 5, Tables: 1, Equations: 0, References: 39, Pages: 9
                Categories
                Research Article

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