Mic1-3 Knockout Toxoplasma gondii is a good candidate for a vaccine against T. gondii-induced abortion in sheep

This study assessed the effectiveness of a mutant strain of Toxoplasma gondii (RH strain) lacking the mic1 and mic3 genes (Mic1-3KO) against Toxoplasma abortion in sheep. Ewes were inoculated subcutaneously with 105 Mic1-3KO tachyzoïtes in three independent experiments. Following vaccination, Mic1-3KO induced a mild febrile response and serum IgG antibodies, which persisted throughout the experiments. Tissue cysts formed in the sheep, but were not, under our experimental conditions, infectious when given orally. Ewes were mated two months after vaccination and were orally challenged with the PRU strain of T. gondii at mid-gestation (400 oocysts in Experiments 1 and 2; 100 oocysts in Experiment 3). Challenge of vaccinated pregnant ewes resulted in a slight febrile response, whereas unvaccinated ewes developed a more severe, characteristic febrile response of longer duration. After challenge, all unvaccinated ewes aborted whereas 62%, 91% and 64% (Experiments 1, 2 and 3 respectively) of the lambs from vaccinated ewes were viable, with no clinical signs of infection. Mic1-3KO was as effective as S48, the strain used as a live vaccine for sheep (Toxovax®). A dose of 105 Mic1-3KO tachyzoites was sufficient to induce protection (versus a dose of 2 × 106). Both subcutaneous and intraperitoneal injections were effective. Moreover, preliminary results showed the potential of Mic1-3KO to reduce the development of tissue cysts in lambs born to vaccinated ewes. This study demonstrates that Mic1-3KO is a potent vaccine candidate

Babesia divergens glycosylphosphatidylinositols modulate blood coagulation and induce Th2-biased cytokine profiles in antigen presenting cells

This work was supported by the the University of Tours (to IDP and FDG), the University of Montpellier (to SD and EC), the Deutsche Forschungsgemeinschaft (to RTS), the Wellcome Trust project grant 093228 (to TKS) and the Campus France/DAAD PHC PROCOPE 24931RE (to RTS and EC). The funding source has no involvement in the conduct of the research and preparation of the article.Glycosylphosphatidylinositols (GPIs) are glycolipids described as toxins of protozoan parasites due to their inflammatory properties in mammalian hosts characterized by the production of interleukin (IL)-1, IL-12 and tumor necrosis factor (TNF)-α. In the present work, we studied the cytokines produced by antigen presenting cells in response to ten different GPI species extracted from Babesia divergens, responsible for babesiosis. Interestingly, B. divergens GPIs induced the production of anti-inflammatory cytokines (IL-2, IL-5) and of the regulatory cytokine IL-10 by macrophages and dendritic cells. In contrast to all protozoan GPIs studied until now, GPIs from B. divergens did not stimulate the production of TNF-α and IL-12, leading to a unique Th1/Th2 profile. Analysis of the carbohydrate composition of the B. divergens GPIs indicated that the di-mannose structure was different from the evolutionary conserved tri-mannose structure, which might explain the particular cytokine profile they induce. Expression of major histocompatibility complex (MHC) molecules on dendritic cells and apoptosis of mouse peritoneal cells were also analysed. B. divergens GPIs did not change expression of MHC class I, but decreased expression of MHC class II at the cell surface, while GPIs slightly increased the percentages of apoptotic cells. During pathogenesis of babesiosis, the inflammation-coagulation auto-amplification loop can lead to thrombosis and the effect of GPIs on coagulation parameters was investigated. Incubation of B. divergens GPIs with rat plasma ex vivo led to increase of fibrinogen levels and to prolonged activated partial thromboplastin time, suggesting a direct modulation of the extrinsic coagulation pathway by GPIs.Publisher PDFPeer reviewe

<em>Toxoplasma gondii</em>: qualified to secrete exosomes?

International audienceToxoplasma gondii is a protozoan parasite responsible for toxoplasmosis, a worldwide disease that leads to encephalitis in immune-compromised individuals and to congenital toxoplasmosis of infected fetus. In order to design effective vaccine strategy a more comprehensive understanding of the biology of Toxoplasmahost interactions is crucial. T. gondii, as eukaryotic cell, contains an endomembrane network including an endoplasmic reticulum and a single Golgi stack. A Rab5 protein-like, localized to tubovesicular structures adjacent to but distinct from the Golgi, is involved in the parasite cholesterol pathway. T. gondii apicoplast expresses Rab7 late endosomal marker. Moreover, Toxoplasma rhoptries, secretory organelles essential for cell invasion, present certain features of lysosomal secretory pathway. These data suggest that, among all these parasite secretory pathways, one could be dedicated to exosomal secretion. Using TEM, we observed Toxoplasma secretory organelles and detected MVB-like structure containing 65-nm vesicles confirming this hypothesis. We purified by sucrose cushion vesicles from peritoneal fluid of Toxoplasma-infected mice, which displayed biochemical and morphological characteristics of exosomes. Immunostaining with colloidal gold indicated the presence of Toxoplasma-specific proteins and proteomic analysis revealed the presence of exosomal markers (Tsp7, Tsp18, CD82, Rab5 and Rab11) and specific Toxoplasma proteins (SAG, MIC, GRA, GPI, ubiquitin and cyclophilin). These results suggest a novel exosomebased pathway as a mechanism of protein secretion used by T. gondii

Toxoplasma gondii: un parasite qualifié pour sécréter des exosomes?

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Toxo KO : un vaccin recombinant vivant pour la prévention de la toxoplasmose congénitale de la brebis

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Development of an innovative subunit vaccine against toxoplasmosis

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Porous nanoparticles as delivery system of complex antigens for an effective vaccine against Toxoplasma gondii infection

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Functional activation of T cells by dendritic cells and macrophages exposed to the intracellular parasite <em>Neospora</em> <em>caninum</em>

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