C Auriault

Institut Pasteur de Lille, Lille, Nord-Pas-de-Calais, France

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Publications (174)566.81 Total impact

  • [Show abstract] [Hide abstract]
    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.
    European Journal of Immunology 12/2004; 34(11):3060-9. · 4.97 Impact Factor
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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.
    International Immunology 10/2004; 16(9):1275-82. · 3.14 Impact Factor
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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.
    Oncogene 05/2004; 23(15):2681-93. · 8.56 Impact Factor
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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.
    Bioconjugate Chemistry 01/2004; 15(2):317-25. · 4.58 Impact Factor
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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.
    Bioconjugate Chemistry 01/2004; 15(2):307-16. · 4.58 Impact Factor
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    ABSTRACT: Gene transfer using immunomodulatory molecules is a promising tool for in vivo regulation of immune responses. Experimental autoimmune uveitis (EAU), which serves as a model for human ocular inflammation, is induced by systemic immunization with autoantigens, but its expression is restricted to the eye. Previously, we reported protection of rodents against EAU by intravenous or/and periocular injection of vIL-10-expressing adenovirus. Here, the expression of vIL-10 was targeted into the rat Lewis eye, by intravitreal injection of either the free virus or ex vivo transfected retinal Müller glial cells (RMG-vIL-10). As shown using GFP-expressing adenovirus, a longer expression of transgene was observed in the eye after transfer of transfected syngeneic RMG cells than was seen after injection of free virus. Intravitreal injection of RMG-vIL-10 led to significant decrease in ocular pathological manifestations, compared to control RMG cells. This was observed when cells were injected simultaneously with autoantigen, but also after a delayed administration of transfected cells. Finally, injection of RMG cells transfected with adenovirus expressing CTLA4 had a strongly protective effect. In conclusion, inhibition of antigen presentation at the site of expression of the autoimmune disorders represents an attractive alternative to treat ocular inflammation, and the transfer of ex vivo genetically modified cells provides a promising method to target the factor of interest into the eye.
    Gene Therapy 12/2003; 10(23):1970-81. · 4.32 Impact Factor
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    ABSTRACT: Index Descriptors and Abbreviations: Schistosoma mansoni; trematode; optical microscopy; coloration
    Experimental Parasitology 01/2003; 104(1-2):74-6. · 2.15 Impact Factor
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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.
    Parasitology International 01/2003; 51(4):367-79. · 2.30 Impact Factor
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    ABSTRACT: Pathological ocular manifestations result from a dysregulation in the balance between proinflammatory type 1 cytokines and regulatory type 2 cytokines. Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent immunosuppressive effects. We have examined the efficiency of viral IL-10 adenovirus (Ad-vIL-10)-mediated gene transfer on experimental autoimmune uveoretinitis (EAU) induced in mice and rats by purified retinal autoantigens, respectively, interphotoreceptor binding protein (IRBP) and S-antigen (S-Ag). B10-A mice that received a single unilateral injection of Ad-vIL-10 in the retro-orbital sinus venosus performed 1 day before immunization with IRBP in the footpads showed high levels of circulating vIL-10 in their sera and a significant reduction in pathological ocular manifestations. Lower levels of IFN-gamma and IL-2 were found in cellular supernatants from IRBP-stimulated splenic cells in these treated mice. The local effect on ocular disease of vIL-10 was neutralized completely by injection of a monoclonal anti-vIL-10 antibody, demonstrating the specificity of the treatment. To determine whether the transfer of the vIL-10 gene within the periocular tissues of the eye could prevent acute EAU, a subconjunctival injection of Ad-vIL-10 was performed in Lewis rats simultaneously with S-antigen in the footpads. This injection determined in situ vIL-10 expression with very low circulating vIL-10 and led to a significant reduction of EAU without affecting the systemic immune response. The present results suggest that Ad-mediated gene transfer resulting in systemic and local expression of vIL-10 provide a promising approach for the treatment of uveitis.
    Clinical & Experimental Immunology 12/2002; 130(2):212-23. · 3.41 Impact Factor
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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.
    Journal of Parasitology 11/2002; 88(5):849-55. · 1.32 Impact Factor
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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.
    Bioorganic & Medicinal Chemistry Letters 11/2002; 12(19):2723-7. · 2.34 Impact Factor
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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.
    Clinical & Experimental Immunology 10/2002; 129(3):429-37. · 3.41 Impact Factor
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    ABSTRACT: Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expression. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and membrane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.
    Journal of Virology 08/2002; 76(13):6460-72. · 5.08 Impact Factor
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    ABSTRACT: We report a novel generation of peptide arrays fabricated by site-specific ligation of glyoxylyl peptides onto glass slides covered by a semicarbazide sol-gel layer. These arrays allowed the highly sensitive and specific detection of antibodies in very small blood samples from infected individuals using three model peptidic epitopes (HCV Core and NS4, EBV Capsid) in an immunofluorescence assay. Comparison with standard enzyme-linked immunosorbent assays (ELISAs) demonstrated a large gain in sensitivity and specificity. These unique properties, combined with the possibility to immobilize glycoproteins such as antibodies, offer the possibility to perform sandwich immunofluorescent assays in a highly parallel format.
    Bioconjugate Chemistry 06/2002; 13(4):713-20. · 4.58 Impact Factor
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    ABSTRACT: The N-terminal part of class II-associated invariant chain peptide (CLIP) is assumed to interact with an accessory peptide-binding site on the class II Major Histocompatibility Complex (MHC) molecule, and promote a conformational modification. We have linked this immunoregulatory segment (residues 81-88) to the N-terminus of the influenza hemagglutinin (HA) 307-319 epitope in order to evaluate relationships between the MHC conformational changes and their implication in immune responses. Our chimeric peptide, named CLIP-HA, bind with the same affinity to class II HLA-DR1 molecules as the HA peptide, and is normally recognized by HA-specific T cells. Interestingly, the presence of the N-terminal CLIP region enhances the rate of association to soluble DR1 molecules but prevents the formation of SDS-resistant complexes. These features suggest the existence of HLA-DR1 conformational changes induced by the chimeric peptide. Furthermore, while in vitro HA and CLIP-HA peptides associated to DR1 could not be differentiated based on T-cell recognition, in vivo the CLIP residues strongly impaired the immunogenicity of HA epitope as assessed in HLA-DR1 transgenic mice. Our study demonstrates for the first time that MHC conformational changes, revealed at molecular level, may influence the immunogenicity.
    Molecular Immunology 03/2002; 38(9):661-7. · 2.65 Impact Factor
  • Journal of Parasitology - J PARASITOL. 01/2002; 88(5):849-855.
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    ABSTRACT: Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expres- sion. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and mem- brane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instru- mental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency. The Epstein-Barr virus (EBV), a member of the herpesvirus family, infects over 90% of healthy adults. EBV classically infects B cells, causing a benign disease, acute infectious mono- nucleosis, but also malignant diseases such as Burkitt's lym- phoma and other B-lymphoproliferative disorders in patients with severe immunodeficiency. EBV can also infect epithelial cells and is associated with undifferentiated nasopharyngeal carcinoma (NPC) (43). More recently, many reports have shown that EBV can be associated with other pathologies, including Hodgkin's disease (HD) (4), lymphoproliferative dis- orders of T cells such as peripheral T-cell lymphoma in immu- nocompetent hosts (6), and gastric, breast, and hepatocellular adenocarcinomas (3, 21). In all the reported cases, the virus displays mainly a latency program of infection with a restricted pattern of gene expression, which can be classified in three types. Type I latency, where only EBNA-1 is expressed, is found in Burkitt's lymphoma. Coexpression of EBNA-1 and latent membrane proteins LMP-1 and LMP-2 is characteristic of a type II latency found in NPC, HD, and T-cell lymphomas, and type III latency with expression of the five EBNAs and three LMPs is found in lymphomas of immunodeficient pa- tients.
    Journal of Virology - J VIROL. 01/2002; 76(13):6460-6472.
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2002; 33(4).
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    ABSTRACT: The mannose receptor mediates the internalization of a wide range of molecules or microorganisms in a pattern recognition manner. Therefore, it represents an attractive entry for specific drug, gene, or antigen delivery to macrophages and dendritic cells. In an attempt to design novel effective synthetic mannose receptor ligands, quinic and shikimic acid were selected as putative mannose mimics on the basis of X-ray crystallographic data from the related rat mannose-binding lectin. As the mannose receptor preferentially binds to molecules displaying several sugar residues, fluorescein-labeled cluster quinic and shikimic acid derivatives with valencies of two to eight were synthesized. Their mannose receptor mediated uptake was assayed on monocyte-derived human dendritic cells by cytofluorimetric analysis. Mannose-receptor specificity was further assessed by competitive inhibition assays with mannan, by confocal microscopy analysis, and by expression of the mannose receptor in transfected Cos-1 cells. Constructs derived from both quinic and shikimic acid were efficiently recognized by the mannose receptor with an optimum affinity for the molecules with a valency of four. As a result, commercially available quinic and shikimic acids appear as stable mannose bioisosteres, which should prove valuable tools for specific cell delivery.
    ChemBioChem 11/2001; 2(10):747-57. · 3.74 Impact Factor
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    ABSTRACT: Genetic factors that might influence susceptibility or resistance in naive individuals and early-stage pathology in schistosomiasis are difficult to study in clinical trials, since in areas where the disease is endemic the first contact with the parasite occurs most often at very early ages. Therefore, four strains (DR1.Abeta degrees, DR2.Abeta degrees, DQ8.Abeta degrees, and DQ6.Abeta degrees ) of major histocompatibility complex class II-deficient mice (Abeta degrees ), transgenic for different HLA alleles, have been used to evaluate the potential role of HLA class II polymorphism in the onset of the infection by Schistosoma mansoni. The survival rates and parasitological and immunological parameters after infection were evaluated and compared against the control values obtained with Abeta degrees mice. All four mouse strains used in this study were able to generate a specific immune response against S. mansoni antigens (cytokine production and antibody production). However, only mice expressing DR alleles survived until the chronic stage of the infection and were able to mount protective granulomatous response avoiding hepatic damage, presenting predominant gamma interferon production. In contrast, strains expressing DQ alleles revealed an impairment in generating effective granulomas, resulting in earlier death, which was associated with an impaired hepatic granulomatous response and liquefactic necrosis, reflecting the influence of HLA polymorphism in the establishment of protective response in the early stage of infection.
    Infection and Immunity 10/2001; 69(9):5874-82. · 4.07 Impact Factor

Publication Stats

2k Citations
566.81 Total Impact Points

Institutions

  • 1980–2014
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1998–2013
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • La Jolla Institute for Allergy & Immunology
      La Jolla, California, United States
  • 2012
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Université René Descartes - Paris 5
      • Laboratoire de Biologie Cellulaire
      Paris, Ile-de-France, France
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 1998–2008
    • Institut de Biologie de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1986–2008
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1995
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1988–1994
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1985–1987
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1982
    • Venezuelan Institute for Scientific Research
      Caracas, Distrito Federal, Venezuela