15 research outputs found

    Status of Coral Reef Communities on Two Carbonate Platforms (Tun Sakaran Marine Park, East Sabah, Malaysia)

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    International audienceThis study concerns three sites, located on carbonate platforms, east Sabah: Gaya West, Gaya East, and Mantabuan. At each site, the dominant coral shapes and their health were recorded (lagoons and outer slopes). Densities of echinoderms, Tridacna, and nudibranchs were recorded while fish density was estimated. Generally, the coral vitality is low (≤50% living corals). Massive corals dominate all sites, except the Gaya West-outer slope where coral coverage and diversity are the highest. On the Mantabuan-mesh reef, a diverse Acropora assemblage dominates the landscape. On the reef flat of Gaya East, monospecific circa 10 meter coral patches occur. Primary producers are scarce on all sites. Sea urchins, dominated by Diadema, are abundant on the Gaya East-reef flat and the Gaya West-mesh reef. Sea stars and holothurids are the most prevalent in Gaya West-outer slope, although they remain scarce. Crinoids are only abundant in Mantabuan. Stegastes damselfish highly characterizes the sites of Gaya East (reef flat and inner slope) and the Mantabuan-mesh reef. On the Mantabuan-outer slope, parrotfish and other fishes are plentiful. No sign of eutrophication has been detected and natural hypersedimentation and/or eventual ancient bleaching events appear to be the direct principal causes of coral death or coral degradation

    Un point sur la pathogénicité des virus influenza: rôle des protéases et de la molécule immunosuppressive HLA-G

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    National audienceLa grippe est une maladie infectieuse, causée par les virus influenza, qui se manifeste par la survenue de grandes pandémies entrecoupées d'épidémies saisonnières. Ces infections récurrentes mettent en évidence la menace permanente causée par ces virus. Face à l'émergence récente de nouvelles souches pandémiques (H1N1 2009) et potentiellement pandémiques (H5N1 aviaire) et de leur diffusion dans le reste du monde, l'objectif de cette revue est d'apporter de nouvelles informations sur les mécanismes de pathogénicité des virus influenza A (IAV). La présence dans les sites infectieux de protéases est un des facteurs majeurs contrôlant le tropisme et l'infectiosité des IAV. Au-delà des effets protéolytiques directs sur les protéines virales, les protéases peuvent également agir sur la cellule hôte via l'activation de récepteurs à sept domaines transmembranaires, dénommés protease activated receptors (PARs). Dans un premier temps, cette revue fait le point sur le rôle des protéases et de leurs récepteurs (annexine II et PAR-2) dans la réplication des IAV. Dans un second temps, la revue fait état des travaux récents menés sur la caractérisation de la molécule non classique du complexe majeur d'histocompatibilité (HLA-G) dont l'expression permettrait de contrôler la réponse immunitaire de l'hôte durant l'infection

    Specificity of the T Cell Response to Protein Biopharmaceuticals.

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    The anti-drug antibody (ADA) response is an undesired humoral response raised against protein biopharmaceuticals (BPs) which can dramatically disturb their therapeutic properties. One particularity of the ADA response resides in the nature of the immunogens, which are usually human(ized) proteins and are therefore expected to be tolerated. CD4 T cells initiate, maintain and regulate the ADA response and are therefore key players of this immune response. Over the last decade, advances have been made in characterizing the T cell responses developed by patients treated with BPs. Epitope specificity and phenotypes of BP-specific T cells have been reported and highlight the effector and regulatory roles of T cells in the ADA response. BP-specific T cell responses are assessed in healthy subjects to anticipate the immunogenicity of BP prior to their testing in clinical trials. Immunogenicity prediction, also called preclinical immunogenicity assessment, aims at identifying immunogenic BPs and immunogenic BP sequences before any BP injection in humans. All of the approaches that have been developed to date rely on the detection of BP-specific T cells in donors who have never been exposed to BPs. The number of BP-specific T cells circulating in the blood of these donors is therefore limited. T cell assays using cells collected from healthy donors might reveal the weak tolerance induced by BPs, whose endogenous form is expressed at a low level. These BPs have a complete human sequence, but the level of their endogenous form appears insufficient to promote the negative selection of autoreactive T cell clones. Multiple T cell epitopes have also been identified in therapeutic antibodies and some other BPs. The pattern of identified T cell epitopes differs across the antibodies, notwithstanding their humanized, human or chimeric nature. However, in all antibodies, the non-germline amino acid sequences mainly found in the CDRs appear to be the main driver of immunogenicity, provided they can be presented by HLA class II molecules. Considering the fact that the BP field is expanding to include new formats and gene and cell therapies, we face new challenges in understanding and mastering the immunogenicity of new biological products

    HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: The influence of the tumor microenvironment

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    International audienceDimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibitingthe antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols
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