8 research outputs found
IMPACT OF CHRONIC TOXOPLASMA GONDII INFECTION ON THE ONSET AND PROGRESSION OF ALZHEIMERâS DISEASE
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons
International audienceControl of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the CNS. We show that MHC I presentation of an efficiently processed model antigen (GRA6-OVA), even when not expressed in the bradyzoite stage, reduces cyst burden and dampens encephalitis in C57BL/6 mice. Antigen presentation assays with infected primary neurons reveal a correlation between lower MHC I presentation of tachyzoite antigens by neurons and poor parasite control in vivo. Using conditional MHC I-deficient mice, we find that neuronal MHC I presentation is required for robust restriction of T. gondii in the CNS during chronic phase, showing the importance of MHC I presentation by CNS neurons in the control of a prevalent brain pathogen
Borna Disease Virus 1 Phosphoprotein Forms a Tetramer and Interacts with Host Factors Involved in DNA Double-Strand Break Repair and mRNA Processing
International audienceDetermining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among Mononegavirales, bornaviruses (family Bornaviridae) stand out due to their compact genomes and their nuclear localisation for replication. The recent recognition of the zoonotic potential of several orthobornaviruses has sparked a surge of interest in improving our knowledge on this viral family. In this work, we provide a complete analysis of the structural organisation of Borna disease virus 1 (BoDV-1) phosphoprotein (P), an important cofactor for polymerase activity. Using X-ray diffusion and diffraction experiments, we revealed that BoDV-1 P adopts a long coiled-coil α-helical structure split into two parts by an original ÎČ-strand twist motif, which is highly conserved across the members of whole Orthobornavirus genus and may regulate viral replication. In parallel, we used BioID to determine the proximal interactome of P in living cells. We confirmed previously known interactors and identified novel proteins linked to several biological processes such as DNA repair or mRNA metabolism. Altogether, our study provides important structure/function cues, which may improve our understanding of BoDV-1 pathogenesis
Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy
La PlanÚte Revisitée en Corse. Expéditions terrestres 2021 - CÎte orientale et <i>Capicorsu</i>: Bilan scientifique
"The Planet Reviewed in Corsica" is an expedition by the MNHN in partnership with the CollectivitĂ© de Corse and the French Office for Biodiversity. Between 2019 and 2022, several teams of scientists are undertaking an inventory of terrestrial and marine diversity of Corsica. The objective is to establish a reference state of a series of sites of high biological value and to modernize the collections of the MNHN. This report provides a quick overview of terrestrial expeditions from two emblematic sectors of Corsica: the west coast and northern Capicorsu. From March to May 2021, 34 participants took part of the inventory of about 10 sites. In 2021, the increased sampling effort and the first phase of identification made it possible to announce 2 227 inventoried species and 11 346 data uploaded and shared in the national inventory of natural heritage (INPN). This last field year makes an important contribution to the national inventory of natural heritage with 75 species inventoried for the first time in Corsica, 5 new species for France and 12 species expected new to science. Many taxa had not been observed for decades or several for more than a century. This knowledge is being disseminated on OpenObs, the French portal for biodiversity. Moreover, the Barcoding campaign achieved a total of 2 200 specimens sequenced for DNA (CO1 et ITS). The results will contribute to the species identifications, the taxonomic revisions to be published but also to enrich the global Barcode of Life information system.« La PlanĂšte RevisitĂ©e en Corse » est une expĂ©dition du MusĂ©um national dâhistoire naturelle menĂ©e en partenariat avec la CollectivitĂ© de Corse et lâOffice français de la BiodiversitĂ©. Entre 2019 et 2021, plusieurs Ă©quipes de scientifiques entreprennent lâinventaire de diffĂ©rents secteurs terrestres et marins reprĂ©sentatifs de la diversitĂ© de Corse afin dâĂ©tablir un Ă©tat de rĂ©fĂ©rence dâune sĂ©rie de sites Ă forte valeur biologique et de moderniser les collections dâhistoire naturelle de rĂ©fĂ©rence du MusĂ©um national. Ce rapport propose un premier bilan « Ă chaud » des expĂ©ditions terrestres de deux secteurs emblĂ©matiques de lâĂźle : la cĂŽte orientale et le nord du Capicorsu. De mars Ă mai 2021, 34 personnes ont participĂ© Ă lâinventaire dâune dizaine de sites. En 2021, lâeffort important dâĂ©chantillonnage et la premiĂšre phase dâidentification permettent dâores et dĂ©jĂ dâannoncer plus de 2 227 espĂšces inventoriĂ©es et 11 346 donnĂ©es mises en ligne et partagĂ©es. Cette troisiĂšme et derniĂšre annĂ©e de terrain apporte une contribution importante Ă lâinventaire du patrimoine naturel avec 12 nouvelles espĂšces pour la science, 75 espĂšces inventoriĂ©es pour la premiĂšre fois en Corse et au moins 5 espĂšces nouvelles pour la France. De nombreux taxons nâavaient pas Ă©tĂ© observĂ©s depuis plusieurs dĂ©cennies voire plus dâun siĂšcle pour certains. Cette connaissance est en cours de diffusion sur OpenObs, le portail d'accĂšs aux donnĂ©es d'observation sur les espĂšces. En parallĂšle, la campagne de codes-barres ADN (CO1 et ITS) de 2021 a permis de sĂ©quencer 2 200 individus. Les rĂ©sultats permettront de contribuer aux dĂ©terminations pour les inventaires, aux rĂ©visions taxinomiques qui feront lâobjet de publications scientifiques mais Ă©galement dâenrichir le systĂšme dâinformation global Barcode of Life
La PlanÚte Revisitée en Corse. Expéditions terrestres 2021 - CÎte orientale et <i>Capicorsu</i>: Bilan scientifique
"The Planet Reviewed in Corsica" is an expedition by the MNHN in partnership with the CollectivitĂ© de Corse and the French Office for Biodiversity. Between 2019 and 2022, several teams of scientists are undertaking an inventory of terrestrial and marine diversity of Corsica. The objective is to establish a reference state of a series of sites of high biological value and to modernize the collections of the MNHN. This report provides a quick overview of terrestrial expeditions from two emblematic sectors of Corsica: the west coast and northern Capicorsu. From March to May 2021, 34 participants took part of the inventory of about 10 sites. In 2021, the increased sampling effort and the first phase of identification made it possible to announce 2 227 inventoried species and 11 346 data uploaded and shared in the national inventory of natural heritage (INPN). This last field year makes an important contribution to the national inventory of natural heritage with 75 species inventoried for the first time in Corsica, 5 new species for France and 12 species expected new to science. Many taxa had not been observed for decades or several for more than a century. This knowledge is being disseminated on OpenObs, the French portal for biodiversity. Moreover, the Barcoding campaign achieved a total of 2 200 specimens sequenced for DNA (CO1 et ITS). The results will contribute to the species identifications, the taxonomic revisions to be published but also to enrich the global Barcode of Life information system.« La PlanĂšte RevisitĂ©e en Corse » est une expĂ©dition du MusĂ©um national dâhistoire naturelle menĂ©e en partenariat avec la CollectivitĂ© de Corse et lâOffice français de la BiodiversitĂ©. Entre 2019 et 2021, plusieurs Ă©quipes de scientifiques entreprennent lâinventaire de diffĂ©rents secteurs terrestres et marins reprĂ©sentatifs de la diversitĂ© de Corse afin dâĂ©tablir un Ă©tat de rĂ©fĂ©rence dâune sĂ©rie de sites Ă forte valeur biologique et de moderniser les collections dâhistoire naturelle de rĂ©fĂ©rence du MusĂ©um national. Ce rapport propose un premier bilan « Ă chaud » des expĂ©ditions terrestres de deux secteurs emblĂ©matiques de lâĂźle : la cĂŽte orientale et le nord du Capicorsu. De mars Ă mai 2021, 34 personnes ont participĂ© Ă lâinventaire dâune dizaine de sites. En 2021, lâeffort important dâĂ©chantillonnage et la premiĂšre phase dâidentification permettent dâores et dĂ©jĂ dâannoncer plus de 2 227 espĂšces inventoriĂ©es et 11 346 donnĂ©es mises en ligne et partagĂ©es. Cette troisiĂšme et derniĂšre annĂ©e de terrain apporte une contribution importante Ă lâinventaire du patrimoine naturel avec 12 nouvelles espĂšces pour la science, 75 espĂšces inventoriĂ©es pour la premiĂšre fois en Corse et au moins 5 espĂšces nouvelles pour la France. De nombreux taxons nâavaient pas Ă©tĂ© observĂ©s depuis plusieurs dĂ©cennies voire plus dâun siĂšcle pour certains. Cette connaissance est en cours de diffusion sur OpenObs, le portail d'accĂšs aux donnĂ©es d'observation sur les espĂšces. En parallĂšle, la campagne de codes-barres ADN (CO1 et ITS) de 2021 a permis de sĂ©quencer 2 200 individus. Les rĂ©sultats permettront de contribuer aux dĂ©terminations pour les inventaires, aux rĂ©visions taxinomiques qui feront lâobjet de publications scientifiques mais Ă©galement dâenrichir le systĂšme dâinformation global Barcode of Life
The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation
International audienceK idney transplantation is the only curative treatment for end-stage renal disease 1. The fact that the first successful kidney transplantation in man was between identical twins 2 , along with seminal work in animal models, hinted strongly that a single genetic locus does not govern the clinical outcome of a transplantation, no matter how relevant (such as the major histocompatibility complex (MHC), human leukocyte antigen (HLA)). Indeed, George Snell, in his landmark 1948 study 3 (as well as subsequent work by himself, and others), identified several dozen histocompatibility loci in the mouse 4 , although close to none has been identified to date in any species (including man). Fast forward to today, and, owing to the development and refinement of country-and continent-wide allocation processes, perioperative handling of the graft and patients, and selective immunosuppressive drugs that improve transplantation survival mainly by alleviating acute T cell-mediated rejection (TCMR), the number of kidney transplantations is continuously increasing worldwide. However, antibody-mediated rejection (ABMR) is recognized as a major cause of late transplantation failure, and its treatment remains challenging 5. In addition to the histological findings, a key feature of ABMR is the presence of donor-specific anti-HLA antibodies (DSA) 6. Nonetheless, in routine clinical care, cases meeting the histological criteria for ABMR but without detectable anti-HLA DSA could represent more than 50% of rejection events 7. These cases might be explained by the presence of pathogenic antibodies that are produced against other, non-HLA, histocompatibility antigens 8. MHC class I chain-related gene A (MICA; GenBank accession: NM_001177519), discovered almost 30 years ago 9 , encodes a polymorphic non-conventional MHC-encoded class I molecule 10. The MICA gene is located, within the HLA complex, 46 kb centromeric to the HLA-B locus 9. Close to 400 MICA alleles have been reported to date 10. The MICA glycoprotein (Uniprot accession: Q96QC4) is expressed on a restricted number of cell types, mainly epithelial and endothelial cells. MICA binds NKG2D, an activating receptor present on the surface of cytotoxic CD8 + αÎČ and γΎ T lymphocytes as well as certain natural killer (NK) cells 10. Fifteen years ago Zou et al. 11 reported the first comprehensive study of the potential involvement of MICA in kidney transplant outcomes. That work, however, was focused only on anti-MICA antibodies and had no information on donor and recipient MICA (mis)matching, a situation that has persisted to date given that no study has analyzed simultaneously the sequence-based molecular MICA matching and the status of both anti-HLA and anti-MICA DSA in a large cohort for which information about all other relevant covariates was available and included in the final analysis (for review see refs. 12,13)