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 β-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

La Planète Revisitée en Corse. Expéditions terrestres 2021 - Côte orientale et <i>Capicorsu</i>: Bilan scientifique

"The Planet Reviewed in Corsica" is an expedition by the MNHN in partnership with the Collectivité 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 Planète Revisitée en Corse » est une expédition du Muséum national d’histoire naturelle menée en partenariat avec la Collectivité de Corse et l’Office français de la Biodiversité. Entre 2019 et 2021, plusieurs équipes de scientifiques entreprennent l’inventaire de différents secteurs terrestres et marins représentatifs de la diversité de Corse afin d’établir un état de référence d’une série de sites à forte valeur biologique et de moderniser les collections d’histoire naturelle de référence du Muséum national. Ce rapport propose un premier bilan « à chaud » des expéditions terrestres de deux secteurs emblématiques de l’île : la côte orientale et le nord du Capicorsu. De mars à mai 2021, 34 personnes ont participé à l’inventaire d’une dizaine de sites. En 2021, l’effort important d’échantillonnage et la première phase d’identification permettent d’ores et déjà d’annoncer plus de 2 227 espèces inventoriées et 11 346 données mises en ligne et partagées. Cette troisième et dernière année de terrain apporte une contribution importante à l’inventaire du patrimoine naturel avec 12 nouvelles espèces pour la science, 75 espèces inventoriées pour la première fois en Corse et au moins 5 espèces nouvelles pour la France. De nombreux taxons n’avaient pas été observés depuis plusieurs décennies voire plus d’un siècle pour certains. Cette connaissance est en cours de diffusion sur OpenObs, le portail d'accès aux données d'observation sur les espèces. En parallèle, la campagne de codes-barres ADN (CO1 et ITS) de 2021 a permis de séquencer 2 200 individus. Les résultats permettront de contribuer aux déterminations pour les inventaires, aux révisions taxinomiques qui feront l’objet de publications scientifiques mais également d’enrichir le système d’information global Barcode of Life

La Planète Revisitée en Corse. Expéditions terrestres 2021 - Côte orientale et <i>Capicorsu</i>: Bilan scientifique

"The Planet Reviewed in Corsica" is an expedition by the MNHN in partnership with the Collectivité 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 Planète Revisitée en Corse » est une expédition du Muséum national d’histoire naturelle menée en partenariat avec la Collectivité de Corse et l’Office français de la Biodiversité. Entre 2019 et 2021, plusieurs équipes de scientifiques entreprennent l’inventaire de différents secteurs terrestres et marins représentatifs de la diversité de Corse afin d’établir un état de référence d’une série de sites à forte valeur biologique et de moderniser les collections d’histoire naturelle de référence du Muséum national. Ce rapport propose un premier bilan « à chaud » des expéditions terrestres de deux secteurs emblématiques de l’île : la côte orientale et le nord du Capicorsu. De mars à mai 2021, 34 personnes ont participé à l’inventaire d’une dizaine de sites. En 2021, l’effort important d’échantillonnage et la première phase d’identification permettent d’ores et déjà d’annoncer plus de 2 227 espèces inventoriées et 11 346 données mises en ligne et partagées. Cette troisième et dernière année de terrain apporte une contribution importante à l’inventaire du patrimoine naturel avec 12 nouvelles espèces pour la science, 75 espèces inventoriées pour la première fois en Corse et au moins 5 espèces nouvelles pour la France. De nombreux taxons n’avaient pas été observés depuis plusieurs décennies voire plus d’un siècle pour certains. Cette connaissance est en cours de diffusion sur OpenObs, le portail d'accès aux données d'observation sur les espèces. En parallèle, la campagne de codes-barres ADN (CO1 et ITS) de 2021 a permis de séquencer 2 200 individus. Les résultats permettront de contribuer aux déterminations pour les inventaires, aux révisions taxinomiques qui feront l’objet de publications scientifiques mais également d’enrichir le système d’information 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 + αβ and γδ 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)