Vaccination against toxoplasmosis in farm animals

Toxoplasmosis is a worldwide zoonotic disease caused by the protozoa Toxoplasma gondii. It is transmitted to man by the ingestion of contaminated and undercooked meat. In sheep and goats, toxoplasmosis causes numerous abortions. A thorough analysis of the seroprevalence of toxoplasmosis in different animal species will help consumer information and thus limit the risks of transmission. The vaccination of farm animals may help reduce the transmission to man, as well as prevent abortion in ewes. A naturally attenuated live T. gondii vaccine is available for the prevention of abortions in ewes, but its virulence is not fully controlled, and there is a risk of reversion to a pathogenic strain. Molecular biology techniques have lead to the development of attenuated strains through the deletion of targeted genes, which are unlikely to revert to their initial virulence. A strain called Mic1-3KO was shown to be effective against congenital and chronic toxoplasmosis in mice. It is also effective against congenital toxoplasmosis in ewes. This vaccine approach remains promising.La toxoplasmose est une zoonose mondialement répandue. Chez l'homme, elle apparaît après l'ingestion de viandes insuffisamment cuites d'animaux contaminés. Chez le mouton et la chèvre, elle est à l'origine de nombreux avortements. Une étude approfondie de sa séroprévalence chez les différentes espèces animales peut permettre de mieux informer les consommateurs et ainsi de limiter les risques de transmission. La vaccination des animaux semble être une alternative intéressante puisqu'elle pourrait diminuer la transmission à l'homme mais également prévenir les avortements chez les brebis. L'utilisation d'une souche naturelle de Toxoplasma gondii incomplète, présentant une virulence atténuée, a montré son efficacité dans la protection contre l'avortement des brebis. Cependant, sa virulence n'est pas bien contrôlée, et le risque de réversion vers la forme virulente existe. Les techniques de biologie moléculaire ont permis d'obtenir des souches atténuées par la délétion de gènes ciblés, qui ne sont pas susceptibles de retrouver leur virulence d'origine. L'une d'elles, appelée Mic1-3KO, a montré son efficacité dans un modèle murin contre la toxoplasmose chronique et congénitale. Elle est également efficace contre la toxoplasmose congénitale chez la brebis. Cette démarche vaccinale reste prometteuse. De plus, l'utilisation du toxoplasme comme vecteur vaccinal reste une perspective intéressante, puisque ce parasite est capable d'exprimer des protéines étrangères

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

Deep maxima of phytoplankton biomass, primary production and bacterial production in the Mediterranean Sea

The deep chlorophyll maximum (DCM) is a ubiquitous feature of phytoplankton vertical distribution in stratified waters that is relevant to our understanding of the mechanisms that underpin the variability in photoautotroph ecophysiology across environmental gradients and has implications for remote sensing of aquatic productivity. During the PEACETIME (Process studies at the air-sea interface after dust deposition in the Mediterranean Sea) cruise, carried out from 10 May to 11 June 2017, we obtained 23 concurrent vertical profiles of phytoplankton chlorophyll a, carbon biomass and primary production, as well as heterotrophic prokaryotic production, in the western and central Mediterranean basins. Our main aims were to quantify the relative role of photoacclimation and enhanced growth as underlying mechanisms of the DCM and to assess the trophic coupling between phytoplankton and heterotrophic prokaryotic production. We found that the DCM coincided with a maximum in both the biomass and primary production but not in the growth rate of phytoplankton, which averaged 0.3 d−1 and was relatively constant across the euphotic layer. Photoacclimation explained most of the increased chlorophyll a at the DCM, as the ratio of carbon to chlorophyll a (C : Chl a) decreased from ca. 90–100 (g : g) at the surface to 20–30 at the base of the euphotic layer, while phytoplankton carbon biomass increased from ca. 6 mgCm−3 at the surface to 10–15 mgCm−3 at the DCM. As a result of photoacclimation, there was an uncoupling between chlorophyll a-specific and carbon-specific productivity across the euphotic layer. The ratio of fucoxanthin to total chlorophyll a increased markedly with depth, suggesting an increased contribution of diatoms at the DCM. The increased biomass and carbon fixation at the base of the euphotic zone was associated with enhanced rates of heterotrophic prokaryotic activity, which also showed a surface peak linked with warmer temperatures. Considering the phytoplankton biomass and turnover rates measured at the DCM, nutrient diffusive fluxes across the nutricline were able to supply only a minor fraction of the photoautotroph nitrogen and phosphorus requirements. Thus the deep maxima in biomass and primary production were not fuelled by new nutrients but likely resulted from cell sinking from the upper layers in combination with the high photosynthetic efficiency of a diatom-rich, low-light acclimated community largely sustained by regenerated nutrients. Further studies with increased temporal and spatial resolution will be required to ascertain if the peaks of deep primary production associated with the DCM persist across the western and central Mediterranean Sea throughout the stratification season

Plankton networks driving carbon export in the oligotrophic ocean

The biological carbon pump is the process by which CO 2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterized. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria and alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of a few bacterial and viral genes can predict a significant fraction of the variability in carbon export in these regions

Global Trends in Marine Plankton Diversity across Kingdoms of Life

35 pages, 18 figures, 1 table, supplementary information https://doi.org/10.1016/j.cell.2019.10.008.-- Raw reads of Tara Oceans are deposited at the European Nucleotide Archive (ENA). In particular, newly released 18S rRNA gene metabarcoding reads are available under the number ENA: PRJEB9737. ENA references for the metagenomics reads corresponding to the size fraction < 0.22 μm (for prokaryotic viruses) analyzed in this study are included in Gregory et al. (2019); see their Table S3. ENA references for the metagenomics reads corresponding to the size fraction 0.22-1.6/3 μm (for prokaryotes and giruses) correspond to Salazar et al. (2019) (see https://zenodo.org/record/3473199). Imaging datasets from the nets are available through the collaborative web application and repository EcoTaxa (Picheral et al., 2017) under the address https://ecotaxa.obs-vlfr.fr/prj/412 for regent data, within the 3 projects https://ecotaxa.obs-vlfr.fr/prj/397, https://ecotaxa.obs-vlfr.fr/prj/398, https://ecotaxa.obs-vlfr.fr/prj/395 for bongo data, and within the 2 projects https://ecotaxa.obs-vlfr.fr/prj/377 and https://ecotaxa.obs-vlfr.fr/prj/378 for WP2 data. A table with Shannon values and multiple samples identifiers, plus a table with flow cytometry data split in six groups are available (https://doi.org/10.17632/p9r9wttjkm.1). Contextual data from the Tara Oceans expedition, including those that are newly released from the Arctic Ocean, are available at https://doi.org/10.1594/PANGAEA.875582The ocean is home to myriad small planktonic organisms that underpin the functioning of marine ecosystems. However, their spatial patterns of diversity and the underlying drivers remain poorly known, precluding projections of their responses to global changes. Here we investigate the latitudinal gradients and global predictors of plankton diversity across archaea, bacteria, eukaryotes, and major virus clades using both molecular and imaging data from Tara Oceans. We show a decline of diversity for most planktonic groups toward the poles, mainly driven by decreasing ocean temperatures. Projections into the future suggest that severe warming of the surface ocean by the end of the 21st century could lead to tropicalization of the diversity of most planktonic groups in temperate and polar regions. These changes may have multiple consequences for marine ecosystem functioning and services and are expected to be particularly significant in key areas for carbon sequestration, fisheries, and marine conservationTara Oceans (which includes both the Tara Oceans and Tara Oceans Polar Circle expeditions) would not exist without the leadership of the Tara Ocean Foundation and the continuous support of 23 institutes (https://oceans.taraexpeditions.org/). We further thank the commitment of the following sponsors: CNRS (in particular Groupement de Recherche GDR3280 and the Research Federation for the Study of Global Ocean Systems Ecology and Evolution FR2022/Tara Oceans-GOSEE), the European Molecular Biology Laboratory (EMBL), Genoscope/CEA, the French Ministry of Research, and the French Government “Investissements d’Avenir” programs OCEANOMICS (ANR-11-BTBR-0008), FRANCE GENOMIQUE (ANR-10-INBS-09-08), MEMO LIFE (ANR-10-LABX-54), the PSL∗ Research University (ANR-11-IDEX-0001-02), as well as EMBRC-France (ANR-10-INBS-02). Funding for the collection and processing of the Tara Oceans data set was provided by NASA Ocean Biology and Biogeochemistry Program under grants NNX11AQ14G, NNX09AU43G, NNX13AE58G, and NNX15AC08G (to the University of Maine); the Canada Excellence research chair on remote sensing of Canada’s new Arctic frontier; and the Canada Foundation for Innovation. We also thank agnès b. and Etienne Bourgois, the Prince Albert II de Monaco Foundation, the Veolia Foundation, Region Bretagne, Lorient Agglomeration, Serge Ferrari, Worldcourier, and KAUST for support and commitment. The global sampling effort was enabled by countless scientists and crew who sampled aboard the Tara from 2009–2013, and we thank MERCATOR-CORIOLIS and ACRI-ST for providing daily satellite data during the expeditions. We are also grateful to the countries who graciously granted sampling permission. We thank Stephanie Henson for providing ocean carbon export data and are also grateful to the other researchers who kindly made their data available. We thank Juan J. Pierella-Karlusich for advice regarding single-copy genes. C.d.V. and N.H. thank the Roscoff Bioinformatics platform ABiMS (http://abims.sb-roscoff.fr) for providing computational resources. C.B. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement 835067) as well as the Radcliffe Institute of Advanced Study at Harvard University for a scholar’s fellowship during the 2016-2017 academic year. M.B.S. thanks the Gordon and Betty Moore Foundation (award 3790) and the National Science Foundation (awards OCE#1536989 and OCE#1829831) as well as the Ohio Supercomputer for computational support. S.G.A. thanks the Spanish Ministry of Economy and Competitiveness (CTM2017-87736-R), and J.M.G. is grateful for project RT2018-101025-B-100. F.L. thanks the Institut Universitaire de France (IUF) as well as the EMBRC platform PIQv for image analysis. M.C.B., D.S., and J.R. received financial support from the French Facility for Global Environment (FFEM) as part of the “Ocean Plankton, Climate and Development” project. M.C.B. also received financial support from the Coordination for the Improvement of Higher Education Personnel of Brazil (CAPES 99999.000487/2016-03)Peer Reviewe

Community-Level Responses to Iron Availability in Open Ocean Plankton Ecosystems

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment

Cellules dendritiques et exosomes (protection vaccinale vis-à-vis des formes chronique et congénitale de la toxoplasmose)

Toxoplasma gondii est un parasite protozoaire intracellulaire obligatoire, qui infecte tous les animaux homéothermes, y compris l'homme. De caractère bénin chez les personnes immunocompétentes, la toxoplasmose peut revêtir un caractère de grande sévérité, dans les cas d'immunosuppression et de contamination transplacentaire du foetus. Les travaux de notre laboratoire ont démontré, dans un modèle murin de transfert passif, le rôle clef des cellules dendritiques (CD), cellules présentatrices d'antigènes professionnelles, dans la réponse immune protectrice vis-à-vis du toxoplasme. Un des mécanismes impliqués serait la sécrétion par les CD d'exosomes. Ces vésicules dérivées des endosomes tardifs présentent des molécules de CMH I et II à leur surface et expriment également une protéine particulière : la lactadhérine pouvant servir dans l'adressage de ces vésicules vers les CD. Ces exosomes sont donc capables de stimuler des lymphocytes T de manière spécifique. Suite à l'établissement d'une lignée de CD spléniques de souris CBA/J (lignée SRDC), CD à caractère phénotypique CD8+, nous avons pu observer que le transfert passif de SRDC ou de ses exosomes sensibilisées par des extraits antigéniques toxoplasmiques (ET), à des souris syngéniques par voie intra veineuse ou sous-cutanée, induit une protection sensible de ces souris contre la toxoplasmose. Cette protection caractérisée par une diminution de la charge parasitaire cérébrale (de 60 à 75 %) est associée à une réponse humorale spécifique sérique (IgG de type IgG2a) et locale (IgA muqueuses) ainsi qu'à une réponse cellulaire (prolifération cellulaire des cellules de rate et de ganglions mésentériques en présence d'ET avec sécrétion spécifique de cytokines de type Th1 (IL-2 et IFN-g) modulé Th2 (IL-4 et IL-10). Dans un dernier temps, nous avons voulu valider ces résultats en modèle de toxoplasmose congénitale. Les souriceaux issus de mères immunisées sont eux-mêmes protégés (croissance et poids quasi normaux, diminution de la charge parasitaire cérébrale) alors que les souriceaux issus de mères témoin sont fortement infectés et présentent les symptômes d'une toxoplasmose congénitale. En conclusion, ces résultats nous permettent d'envisager l'élaboration d'une stratégie vaccinale anti-toxoplasmique nouvelle et rationnelle basée sur l'utilisation de CD ou d'exosomes comme adjuvants de l'immunité.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Toxoplasma gondii: un parasite qualifié pour sécréter des exosomes?

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