C Auriault

University of Lille Nord de France, Lille, Nord-Pas-de-Calais, France

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Publications (184)577.49 Total impact

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    ABSTRACT: Introduction : Cirrhosis due to hepatitis C virus (HCV) is a common indication for liver transplantation. HCV infection of the graft is universal, and liver damage is accelerated, with cirrhosis occurring in 10-30% of patients within five years. Failure of immune response during HCV primo-infection in non transplanted patients is associated with increased regulatory T cells (CD4+CD25+) activity. The aim of this study was to evaluate the implication of regulatory T cells during HCV recurrence after liver transplantation. Patients and Methods : Different regulatory T cells sub-populations were evaluated using transcriptomic analysis of serum and liver samples from patients 5 years after transplantation. The analysis of 23 regulatory T cells associated genes was performed. Three groups of patients have been evaluated : stable liver recipients without HCV infection (n = 8), liver recipients with minimal hepatitis C recurrence (METAVIR ≤A1F2, n = 10) and patients with severe recurrence (METAVIR> A1F2, n = 10). Results : The expression of markers associated with T CD4+CD25+ sub-population, particularly CD4, CD25, OX40, GITR, and ICAM1 was significantly enhanced in liver recipients with hepatitis C recurrence (p<0.05 versus stable recipients). Markers co-expressed by T regulatory-1 cells (CD49b, CD18) were over-expressed in patients with severe hepatitis C recurrence when compared to minimal hepatitis C recurrence or stable recipients (p<0.05). Moreover, expression of immunosuppressive cytokines, IL-10 and TGF- was significantly increased during HCV recurrence. This latter result was confirmed in situ by immunohistochemistry and in serum by ELISA assays. Conclusion : Our results suggest, for the first time, that regulatory T cells could be implicated in hepatitis C recurrence following liver transplantation. Identification of regulatory T cells sub-populations able to modulate liver injury could give important insights in order to elaborate new therapeutic strategies.
    No preview · Conference Paper · Oct 2006
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    ABSTRACT: Epstein-Barr virus (EBV) is associated with several human malignancies where it expresses limited subsets of latent proteins. Of the latent proteins, latent membrane protein 1 (LMP1) is a potent transforming protein that constitutively induces multiple cell signaling pathways and contributes to EBV-associated oncogenesis. Regulation of LMP1 expression has been extensively described during the type III latency of EBV. Nevertheless, in the majority of EBV-associated tumors, the virus is commonly found to display a type II latency program in which it is still unknown which viral or cellular protein is really involved in maintaining LMP1 expression. Here, we demonstrate that LMP1 activates its own promoter pLMP1 through the JNK signaling pathway emerging from the TES2 domain. Our results also reveal that this activation is tightly controlled by LMP1, since pLMP1 is inhibited by LMP1-activated NF-κB signaling pathway. By using our physiological models of EBV-infected cells displaying type II latency as well as lymphoblastoid cell lines expressing a type III latency, we also demonstrate that this balanced autoregulation of LMP1 is shared by both latency programs. Finally, we show that this autoactivation is the most important mechanism to maintain LMP1 expression during the type II latency program of EBV.
    Full-text · Article · Sep 2006 · Journal of Virology
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    Full-text · Article · Aug 2006
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    ABSTRACT: The identification of MHC class II-restricted peptides has become a priority for the development of peptide-based prophylactic and therapeutic vaccines. The aim of this study was to assess the correlations between peptide-binding assays on purified HLA II molecules and immunization of human HLA II transgenic mice deficient in murine class II molecules (Abeta degrees ). We used as models two MHC class II-restricted peptides, one derived from the HIV Nef regulatory protein (Nef (56-68)) and the other from the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST (190-211)). High correlations were found between the two approaches, which showed that the Nef (56-68) and Sm28GST (190-211) peptides may represent promiscuous ligands for HLA-DQ and for HLA-DR molecules, respectively. We suggest a rational method based on the combination of peptide-binding assays and HLA II transgenic mice experiments as consistent and complementary tools for selecting T helper epitopes.
    No preview · Article · Apr 2006 · Vaccine
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    ABSTRACT: Interleukin (IL-)7 and thyroxin (T4) favor Schistosoma mansoni development. Their effect is similar, rather than identical; moreover, cotreatment acts synergistically on parasites. This questioned a common mediator to their action, which we hypothesized was host glucose metabolism. Infection with S. mansoni resulted in an early peak in glycemia immediately followed by a peak of insulinemia (D7-21). In IL-7 + T4 cotreated infected animals, the peak of insulin was abrogated. We further assessed the consequences of experimentally induced glucose- or insulin-level variations on parasite development. Insulin treatment from day 14 to day 21 post-infection (PI) led to increased worm burden and parasite size, thus mimicking the effect of T4 on schistosome development. Interestingly, insulin treatment did not modify glycemia yet abrogated the hyperinsulinemia, normally occurring during infection. Finally, these treatments were associated with an alteration of the expression of parasite genes involved in glucose uptake. These experiments characterize the elaborate links between parasite and host metabolism and their reciprocal influences.
    No preview · Article · Sep 2005 · Journal of Parasitology
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    ABSTRACT: New vaccines based on subunits, synthetic peptides, or DNA need innovative adjuvants or antigen delivery systems: Spherulites are multilamellar vesicles made of incompatible lipid bilayers without any aqueous core. In this study, we evaluated their ability to induce immune responses against human serum albumin (HSA). Mice were immunized by the intraperitoneal/intravenous route or subcutaneously with HSA without any adjuvant or in its encapsulated form. We showed that Spherulites strongly enhanced the seric antibody responses and led to a mixed isotypic distribution characterized by an IgG(2a) potentiation. This demonstrated that Spherulites can improve the presentation of weak antigens to the immune system.
    No preview · Article · Mar 2005 · Drug Delivery
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    ABSTRACT: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice were created and their immunological potential evaluated in response to hepatitis B DNA vaccine. Every single immunized mouse developed hepatitis B virus-specific antibodies, HLA-DR1-restricted helper, and HLA-A2.1-restricted cytolytic T cell responses directed at the same immunodominant epitopes as those identified in naturally infected or vaccinated humans. These mice were specifically protected against a hepatitis B-recombinant vaccinia virus infection with a 10,000-fold or more reduction of the virus load at day 4 post-challenge. These mice represent a unique in vivo experimental model for human immune function studies without any interference with mouse MHC response which dwarfed the prediction of human responses. Furthermore, they enable the complete monitoring of immune adaptative responses for preclinical screening of candidate vaccines.
    Full-text · Article · Dec 2004 · European Journal of Immunology
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    ABSTRACT: Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted antigen-specific responses in transgenic mice, by favoring murine over human MHC recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease.
    Full-text · Article · Oct 2004 · International Immunology
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    ABSTRACT: The latent membrane protein-1 (LMP1) is an integral membrane molecule expressed by Epstein-Barr virus (EBV) during viral latency and displays properties of a constitutively activated member of the TNF receptor family. LMP1 is required for B-cell or monocyte immortalization induced by EBV and is sufficient to transform rodent fibroblasts. Transforming potential of LMP1 is mediated by its cytoplasmic C-terminal domain, which activates various cellular signaling pathways including NFkappaB and JNK. In this report, we constructed mutants of LMP1 with preserved membrane spanning domain but mutated in the C-terminal domain and a second truncated C-terminal LMP1 fused to the enhanced green fluorescent protein. This latter mutant, termed LMP1-CT, impairs signaling by ectopic LMP1 as well as endogenous EBV-expressed wild-type (wt) LMP1. In contrast to dominant-negative mutants of LMP1 with preserved membrane spanning domains, LMP1-CT was unable to bind wt LMP1 to form an inactive complex. Its dominant-negative effects were due to binding and sequestration of LMP1 adapters TRAF2 and TRADD as assessed by coimmunoprecipitation experiments and confocal analysis. The effect was selective since LMP1-CT did not inhibit IL-1beta-induced signaling, whereas it impaired TNF-triggered NFkappaB and JNK signals without affecting TNF-induced apoptosis. In addition and in contrast to LMP1 constructs with membrane localization, LMP-CT did not display cytostatic properties in noninfected cells. Importantly, LMP1-CT inhibited survival induced by LMP1 in an EBV-transformed T-cell line expressing the type II viral latency commonly found in the majority of EBV-associated human tumors. These data demonstrate that LMP1-CT is a new tool to explore the differences between LMP1 and TNF signaling and may facilitate the design of molecules with potential therapeutic roles.
    Full-text · Article · May 2004 · Oncogene
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    ABSTRACT: We have described in the accompanying article the preparation of peptide-protein semicarbazide microarrays and their use for the simultaneous serodetection of antibodies directed against different pathogens. Here, we present a comparative study between semicarbazide and amine glass slides in an immunofluorescent serodetection assay using HIV (Gp120, Gp41), HCV (mix-HCV, core, NS3, and NS4), and HBV (HBs) recombinant antigens. Amine and semicarbazide surfaces displayed the same sensitivity for antibodies detection just after printing. However, the reactivity of protein antigens changed rapidly upon aging on amine slides but not on semicarbazide slides. Peptide or protein semicarbazide microarrays were found to be remarkably stable for months. Additional data concerning the characterization of the semicarbazide surface (homogeneity of the slides, chemical stability, contact angle measurements, atomic force microscopy studies, reproducibility of serodetection results) are also presented and discussed.
    No preview · Article · Mar 2004 · Bioconjugate Chemistry
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    ABSTRACT: We describe novel peptide-protein microarrays, which were fabricated using semicarbazide glass slides that permitted the immobilization of glyoxylyl peptides by site-specific ligation and the immobilization of proteins by physisorption. The arrays permitted the simultaneous serodetection of antibodies directed against hepatitis C virus (HCV core p21 15-45 peptide, NS4 1925-1947 peptide, core, NS3, NS4, and mixture of core, NS3, NS4, and NS5 antigens), hepatitis B virus (HBc, HBe, and HBs), human immunodeficiency virus (Gp41 and Gp120 for HIV-I and Gp36 for HIV-II), Epstein-Barr virus (VCAp18 153-176 peptide), and syphilis (rTpN47 and rTpN17) antigens using an immunofluorescence assay. Peptide-protein microarrays displayed high signal-to-noise ratios, sensitivities, and specificities for the detection of antibodies as revealed by the analysis of a collection of human sera referenced against these five pathogens.
    No preview · Article · Mar 2004 · Bioconjugate Chemistry
  • S Depil · O Moralès · C Auriault
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    ABSTRACT: Epstein-Barr virus (EBV) seems to use B cell normal differentiation pathways to establish and maintain a persistent infection. This process is effectively controlled by the immune system through the action of EBV-specific T lymphocytes, so that the lifelong chronic infection is free of complications for most individuals. EBV is, however, associated with several malignancies. 30-50% of Hodgkin's lymphomas (HL) are EBV-associated. In EBV-positive HL, the virus is localized to the tumor cells and is clonal. HL is characterized by a type II form of latency with viral antigen expression limited to EBNA1, LMP1 and LMP2. EBV-positive HL is more frequent in childhood, in older patients and in mixed cellularity cases. EBV association may represent a poor prognosis factor in the elderly. The true contribution of EBV to the pathogenesis of HL remains uncertain, but EBV may provide to abnormal B cells survival signals protecting them from apoptosis. Finally, whatever the role that EBV plays in tumor development, the presence of viral antigens in the malignant cells may represent a target for new therapeutic strategies.
    No preview · Article · Nov 2003 · Annales de biologie clinique
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    ABSTRACT: Index Descriptors and Abbreviations: Schistosoma mansoni; trematode; optical microscopy; coloration
    No preview · Article · May 2003 · Experimental Parasitology
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    ABSTRACT: IL-10 is a cytokine secreted by a wide variety of cell types and has pleiotropic activities, mainly as a modulator of the immune response. In this study, we tested in a direct way the influence of IL-10 expression on Leishmania major infection in resistant mice. We report that C57BL/6 mice treated with a single inoculation of recombinant adenovirus vector-expressing viral IL-10 (Ad-vIL-10), 1 day before parasitic challenge, exhibited a dual effect on footpad swelling, characterized by a decrease on lesion size at the early stage of the infection, followed by a rapid increase of these lesions that attained the complete healing later in infection. The reduction in lesion swelling in vIL-10 treated mice was accompanied by a decrease cellular infiltration of lymphocytes and monocytes at the site of parasite inoculation. Most significantly, vIL-10 administration led to a higher parasite burden in the draining popliteal lymph nodes late during infection, when the complete healing of the lesions was already achieved. RT-PCR analysis showed no important modification of cytokine transcripts in vIL-10 treated mice, early in infection, indicating no changes in mouse phenotype from resistant to susceptible status. Therefore, IL-10 administration influenced the outcome of the disease by modifying the inflammation and local cell recruitment at the site of parasite penetration and by leading to an enhanced residual parasite load in popliteal lymph nodes later in infection. The implication of IL-10 on the host immune status and the establishment and outcome of the infection is discussed.
    No preview · Article · Jan 2003 · Parasitology International
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    ABSTRACT: Schistosoma mansoni induces, in the vertebrate host, cutaneous production of interleukin-7 (IL-7), which is beneficial for parasite establishment and development. Infection of mice deficient in IL-7 expression leads to parasite dwarfism. Because similar findings were previously described in hypothyroid mice, this study aimed to elucidate the potential link between IL-7 and thyroid hormones (THs), using several models including hypo- and hyperthyroid mice, modified either transiently or constitutively. Mice treated with thyroxine led to increased worm numbers and development of giant worms, whereas an iodine-deficient diet reduced parasite maturation, egg laying, and liver pathology. Conversely, mice genetically deficient for either of the nuclear TH receptors displayed normal worm development despite modifications in hormone levels, suggesting that thyroxine action is mediated through host receptors. In addition, no modification of antibody titers has been evidenced in thyroxine-treated mice, whereas antibody levels were altered in transgenic animals. These observations suggest that the immune system is not likely to be involved in the modifications of parasite development reported in this study. Interestingly, concomitant treatment with IL-7 and thyroxine had a synergistic effect, leading to recovery of very large worms, thus raising questions about the complexity of interactions between IL-7 and metabolic hormones.
    No preview · Article · Nov 2002 · Journal of Parasitology
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    ABSTRACT: Effect of charge and shape of multivalent lysine-based cluster glycomimetics on their mannose receptor-mediated uptake by human dendritic cells has been evaluated: The capture is strongly affected by the shape of the ligands. The effect of charge is less pronounced although positive charges on the ligands seem to favor non-specific endocytosis capture.
    Full-text · Article · Nov 2002 · Bioorganic & Medicinal Chemistry Letters
  • Nunzia Benedetto · Claude Auriault
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    ABSTRACT: In the central nervous system, cytokine-primed microglia play a pivotal role in host defence against parasite infections. In this study, the effect of recombinant (r) prolactin (rPRL) and rIFN-gamma on A. castellanii infection in murine microglia was examined. Priming of microglia with rPRL and rIFN-gamma synergistically triggered, in a dose-dependent manner, amebastatic activity and the release of endogenous IL-1alpha, IL-1beta, IL-6 and TNF-alpha. More than 53, 57, 49, 89 or 96 % of amebastatic activity was abrogated by anti-PRLR, IFN-gammaR, IL-1beta (but not IL-1alpha), IL-6 or TNF-alpha antibodies, suggesting that these two receptors and proinflammatory cytokines participate in the anti-microbial function. Inasmuch as DPI and AET, both inhibitors of NO synthase, blocked amebastatic activity only during the priming process, the NO-dependent pathway itself appears not to be directly involved in the anti-parasitic capacity. These data suggest that the PRL/PRLR and IFN-gamma/IFN-gamma/R complexes, by the induction of the IFN-gammaR on microglia, up-regulate the release of endogenous TNF-alpha, IL-6 and IL-1beta by these cells, which could trigger anti-microbial activity against A. castellanii infection in the brain [corrected].
    No preview · Article · Oct 2002 · European cytokine network
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    ABSTRACT: We describe the highly conserved sequence 56-68 of the HIV Nef protein as the first promiscuous HLA-DQ HIV-derived peptide. The Nef peptide exhibits an albeit rare capacity to bind 6 different HLA-DQ molecules whereas no binding is observed with the 10 HLA-DR molecules tested. In agreement with these data, after immunization with the Nef peptide, HLA-DQ transgenic Abeta degrees mice display a vigorous cellular and humoral response while the specific immune response of HLA-DR expressing mice is minimal. The promiscuous potentiality of the Nef 56-68 peptide in humans has been confirmed by ex vivo immunization experiments with CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68 specific CD4+ T cells rapidly acquire a memory cell phenotype and are characterized by the preferential usage of the TCR Vbeta 6.1 gene segment and predominant production of IFN-gamma. Taken together, these data indicate that the Nef 56-68 peptide constitutes an attractive component of vaccines aiming at inducing or enhancing HIV-specific T cell immunity.
    Full-text · Article · Oct 2002 · Clinical & Experimental Immunology

  • No preview · Article · Oct 2002
  • E. Masy · E. Adriaenssens · C. Auriault · J. Coll
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    ABSTRACT: The latent membrane protein-1 (LMP-1) of Epstein-Barr virus (EBV) is a key oncogene for cellular transformation and tumorigenesis by this virus. It is expressed in the majority of tumoral pathologies associated with this virus like nasopharynx carcinoma, Hodgkin disease and some T cell lymphoma. In vitro, LMP-1 expression is essential for establishing lymphoblastoid cell lines (LCLs) after immortalization of B-cell by EBV and for transformation of macrophages by the virus. Its role in proliferation, survival, inhibition of senescence as well as tumorigenicity is further stressed by experiments using ectopic expression in non infected cells or in transgenic mice. LMP-1 is functionally related to members of the TNF receptor (TNFR) family. LMP-1 is thus a constitutively active membrane receptor able to induce the cellular NFκB, JNK, P38 and JAK/STAT signal transduction pathways through recruitment of adapters like TRAFs (TNF receptor associated factor) and TRADD (TNF receptor death domain). This review will focus on the different clues of LMP-1-triggered signal transduction together with phenotypic and transformation outputs.
    No preview · Article · Sep 2002 · Virologie

Publication Stats

4k Citations
577.49 Total Impact Points

Institutions

  • 2014
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 1992-2013
    • French National Centre for Scientific Research
      • Centre de Biophysique Moléculaire
      Lutetia Parisorum, Île-de-France, France
  • 1980-2012
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 1985-2008
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1998-2007
    • Institut de Biologie de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1985-2002
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Pasteur Institute of India
      Raj Nilgiri, Odisha, India
  • 1995
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1988
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France