Tuba regulates stability and symmetry of immune synapses

La synapse immune est une jonction cellulaire organisée qui permet la communication entre lymphocytes T et cellules présentatrices d'antigène et assure l activation contrôlée du lymphocyte T et l exécution de ses fonctions effectrices. La formation de la synapse immune requiert la polarisation du lymphocyte T. Notre étude a porté sur Tuba, une protéine récemment caractérisée qui interagit avec divers partenaires cellulaires impliqués dans la polarité cellulaire et le remaniement du cytosquelette d actine. Nous avons étudié le rôle de Tuba sur la polarisation des lymphocytes T et sur la formation de la synapse immune. Nos résultats indiquent qu en absence de stimuli, les lymphocytes T déplétés de Tuba présentent une forme très polarisée par rapport aux contrôles. Suite à la reconnaissance antigénique, les cellules T forment des contacts avec les cellules présentatrices d antigène moins stables et asymétriques en l absence de Tuba. Des récepteurs, des molécules de signalisation et adhésion se positionnent de manière peu structurée dans la zone de contact. De façon paradoxale, les étapes précoces de l activation lymphocytaire ne sont que faiblement affectées par l absence de Tuba, alors que la production d IL-2 est exacerbée. Nos résultats indiquent que Tuba régule la formation et la stabilisation des contacts entre lymphocyte T et cellule présentatrice d antigène, et intervient dans la coordination de l activation lymphocytaire lors de la formation de la synapse immune. Tuba pourrait moduler la nature et la dynamique des contacts entre cellules ( kinapse versus synapse ) nécessaires à la coordination des étapes précoces et tardives de l activation du lymphocyte.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

De nouvelles structures infectieuses, potentielles cibles thérapeutiques antirétrovirales

La transmission par contact cellulaire est récemment apparue comme le mécanisme de dissémination privilégié des rétrovirus lymphotropes humains. L’étude des structures intercellulaires mises en jeu et la caractérisation du matériel viral infectieux transmis au niveau de ces contacts cellulaires devraient permettre de définir de nouvelles cibles thérapeutiques antirétrovirales

Vesicle traffic to the immunological synapse: a multifunctional process targeted by lymphotropic viruses.

The site of contact between T lymphocytes and antigen-presenting cells becomes, upon antigen recognition, an organized junction named the immunological synapse. Various T cell organelles polarize, together with microtubules, toward the antigen-presenting cell. Among them, intracellular vesicular compartments, such as the Golgi apparatus, the recycling endosomal compartment, or cytotoxic granules help to build the immunological synapse and ensure effector functions, such as polarized secretion of cytokines by helper T cells, or exocytosis of lytic granules by cytotoxic T cells. Lymphotropic retroviruses, such as the human immunodeficiency virus type 1, the human T cell leukemia virus type 1, or the Herpesvirus saimiri, can subvert some of the vesicle traffic mechanisms impeding the generation and function of the immunological synapses. This review focuses on the polarization of vesicle traffic, its regulation, and its role in maintaining the structure and function of the immunological synapse. We discuss how some lymphotropic viruses target the vesicle traffic in T lymphocytes, inhibiting the formation of immunological synapses and modulating the response of infected T cells

Can viruses form biofilms?

International audienceThe recent finding that the human T-cell leukemia virus type 1 (HTLV-1) encases itself in a carbohydrate-rich adhesive extracellular 'cocoon', which enables its efficient and protected transfer between cells, unveiled a new infectious entity and a novel mechanism of viral transmission. These HTLV-1 structures are observed at the surface of T cells from HTLV-1-infected patients and are reminiscent of bacterial biofilms. The virus controls the synthesis of the matrix, which surrounds the virions and attaches them to the T cell surface. We propose that, similar to bacterial biofilms, viral biofilms could represent 'viral communities' with enhanced infectious capacity and improved spread compared with 'free' viral particles, and might constitute a key reservoir for chronic infections

Modulation de l'activité de GSK 3 beta et de la phosphorylation par la kinase PKR

PARIS7-Bibliothèque centrale (751132105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Recyclage polarisé et formation de la synapse immune dans les lymphocytes T

International audienc

Recyclage polarisé et formation de la synapse immune dans les lymphocytes T

International audienc

Recombinant infectious hematopoietic necrosis viruses induce protection for rainbow trout Oncorhynchus mykiss

13 páginas, 8 figuras, 1 tablaInfectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicaemia virus (VHSV) are rhabdoviruses that infect salmonids, producing serious economic losses. Two recombinant IHN viruses were generated by reverse genetics. For one (rIHNV GFP) the IHNV NV gene was replaced with the green fluorescent protein (GFP) gene. In the other (rIHNV-Gvhsv GFP) the G gene was also exchanged for that of VHSV. No mortalities, external signs or histological lesions were observed in experimental infections conducted with the recombinant viruses. Neither the rIHNV GFP nor rIHNV-Gvhsv GFP was detected by RT-PCR in any of the examined tissues from experimentally infected fish. In order to assess their potential as vaccines against the wild type viruses, rainbow trout were vaccinated with the recombinant viruses by intraperitoneal injection and challenged 30 d later with virulent IHNV or VHSV. The GFP viruses provided protection against both wild type viruses. None of the recombinant viruses induced antibody production, and the expression of interferon (IFNαβ) and interferon induced genes such as Mx protein and ISG-15 was not different to that of controls. The rIHNV-Gvhsv GFP did not inhibit cellular apoptosis as it was observed in an IHNV inoculated fish cell line. These studies suggest that the recombinant rIHNV-Gvhsv GFP is a promising candidate as a live recombinant vaccine and also provides a good model to further study viral pathogenicity and the molecular basis of protection against these viral infectionsThis work was supported by the projects FAIRCT 98-4398 from the European Union, BIO 2000-0906 and BIO 2001-2324-C02-01 from the Spanish Ministerio de Ciencia y TecnologíaPeer reviewe