Marie-Lise Gougeon

Marie-Lise Gougeon
Institut Pasteur · Department of Infection and Epidemiology (IE)

Prof.

About

281
Publications
22,674
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12,375
Citations
Citations since 2017
26 Research Items
2956 Citations
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Introduction
Marie-Lise Gougeon is currently the Director of the Infection and Epidemiology (IE) Department, and the Director of the Innate Immunity and Viruses research Unit, Institut Pasteur. Marie-Lise does research in Infectious Diseases, Clinical Trials and Cell Biology. Her most recent publications are: 1- '‘HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Disorders (HAND) (Heliyon, 2017) 2- Alarmins and central nervous system inflammation in HIV-associated neurological disorders (J Intern Med 2017) 3- "Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial" (Lancet Neurology 2017)

Publications

Publications (281)
Article
We report safety (primary endpoint) and efficacy (secondary endpoint) of novel intracerebral gene therapy at 5.5 years of follow-up in children with Sanfilippo B. An uncontrolled phase 1/2 clinical trial was performed in 4 patients aged 20, 26, 30 and 53 months. Treatment consisted in 16 intra-cerebral and cerebellar deposits of a recombinant adeno...
Article
Full-text available
Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent huma...
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Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known...
Article
Background Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for opt...
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Understanding the viral–host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections a...
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Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral...
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Introduction Des études épidémiologiques ont montré un lien entre infection par HPV16 et survenue d’un lichen plan (LP) érosif (LPE). L’existence de lymphocytes T (LT) CD8+ clonaux spécifiques du peptide immunodominant d’HPV16 a été montrée en périphérie et au site lésionnel dans cette forme de LP. Nous avons souhaité tester cette même hypothèse da...
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Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated w...
Article
Subjects and methods: A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-2...
Article
Background Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2–4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intrac...
Article
Introduction Lorsque une personne doit recevoir plusieurs vaccins vivants atténués, il est recommandé de les administrer soit simultanément, soit en respectant un délai minimal de 28 jours entre les deux injections, en raison d’une possible interférence négative sur la réponse immune à chacun de ces vaccins. L’objectif principal de cette étude étai...
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Background HIV-associated neurocognitive disorders (HAND) persist in the post-HAART era, characterized by asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). High mobility group box 1 (HMGB1) is a non-histone chromosomal protein widely expressed in the nucleus of all eukaryotic cells, including brain cells, which a...
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In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus...
Book
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Classically, anti-cancer therapies have always been applied with the primary aim of tumor debulking achieved through widespread induction of cancer cell death. While the role of host immune system is frequently considered as host protective in various (antigen-bearing) pathologies or infections yet in case of cancer overtime it was proposed that th...
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Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected C...
Data
Impact of HIV-1 on the survival of pDCs. pDCs were exposed to HIV-1 (1 and 20 ng/ml) for 24h or incubated in culture medium (NS). pDCs were intracellularly stained with Bcl-2 antibody. Living pDCs were identified as CD123Pos Bcl2high (red) or CD123Pos Bcl2med cell populations. Histogram (right side) shows the mean ± SD of five independent experimen...
Data
Impact of aNK cells on the phenotypic maturation of pDCs. pDCs were cultured for 24 h in the presence or not of aNK cells. Stimulation with CpG (3 μg/ml) was used as positive control. (A): Forward Scatter (FSC) and side-scatter (SSC) parameters were used to discriminate mature pDCs (red) from immature pDCs (blue) under the indicated conditions of s...
Data
HIV-1Ad5 triggers the release of proinflammatory cytokines and chemokines by pDCs. Cytokines and chemokines content were quantified by MAP technology in 24 hour cell-free culture supernatants of pDCs incubated in medium (uninf) or exposed to high concentrations of purified CCR5-HIV strain Ad5 (20 ng/ml p24). The mean values ± SD of four independent...
Data
Expression of TRAIL at the surface of HIV-1-exposed aNK cells. Activated NK cells (aNK cells) were exposed to CpG (3 μg/ml), increasing concentrations of HIV-1, or incubated in culture medium (NS) for 24h. Membrane TRAIL (mTRAIL) expression on aNK cells was monitored by flow cytometry. Results from one representative experiment out of three experim...
Data
Phenotypic characterization of immature and mature pDCs. (A): pDCs were activated for 24h with CpG (3μg/ml), LPS (10 μg/ml), trimeric CD40L (500 ng/ml) or incubated in culture medium (NS). GpC (3μg/ml) was used as a negative control of pDCs maturation. Forward Scatter (FSC) and side-scatter (SSC) parameters were used to discriminate mature pDCs (re...
Data
Proinflammatory cytokines and chemokines released by activated NK cells, pDCs and NK-pDC cocultures. Cytokines and chemokines content were quantified by MAP technology in 24 h cell-free culture supernatants of activated NK cells (aNK cells), pDCs cultivated alone or in the presence of aNK cells. The mean ± SD of at least three independent experimen...
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The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology...
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Background and aims: Data on the efficacy and safety of seasonal influenza vaccines in patients with inflammatory bowel disease (IBD) remain scarce. The aim of the study was to evaluate the impact of immunosuppressive (IS) therapeutics on serological response to 2-year influenza vaccination in IBD adults. Methods: A multicenter prospective study...
Article
Le lichen plan érosif (LPE) est une maladie chronique dysimmunitaire rare et invalidante caractérisée par des lésions muqueuses inflammatoires érosives, avec une infiltration de lymphocytes T cytotoxiques CD8⁺. La spécificité de ces lymphocytes n’a jamais été analysée. Dans le but d’identifier les mécanismes moléculaires sous-jacents, nous avons ét...
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Systemic chemotherapy generally has been considered immunosuppressive, but it has become evident that certain chemotherapeutic drugs elicit immunogenic danger signals in dying cancer cells that can incite protective antitumor immunity. In this study, we investigated whether loco-regionally applied therapies such as melphalan used in limb perfusion...
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Obtaining a comprehensive quantitative figure of the determinants of influenza infection will help identify priority targets for future influenza mitigation interventions. We developed an original causal model integrating highly diverse factors and their dependencies, to identify the most critical determinants of pandemic influenza infection (H1N1p...
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Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as /`accidental cell death/' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correl...
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Erosive oral lichen planus (OLP) is a chronic, disabling muco-cutaneous dysimmune rare disease characterized by mucosal inflammatory erosive lesions with pathological evidence for a marked CD8(+) cytotoxic T-cell (CTL) infiltration. However, the specificity of lesional CTL in OLP has never been analyzed. To investigate the molecular mechanisms unde...
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The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis and transformed t...
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Thimerosal is a preservative used in multidose vials of vaccine formulations to prevent bacterial and fungal contamination. We recently reported that nanomolar concentrations of thimerosal induce cell cycle arrest of human T cells activated via the TCR and inhibition of proinflammatory cytokine production, thus interfering with T-cell functions. Gi...
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Thimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the...
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The type of T cell polarization and simultaneous production of multiple cytokines have been correlated with vaccine efficacy. ELISpot is a T cell detection technique optimized for the measurement of a secreted cytokine at the single cell level. The FluoroSpot assay differs from ELISpot by the use of multiple fluorescent-labeled anticytokine detecti...
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Author Summary Human Mucosa-Associated Invariant T cells (MAIT) detect microbe-derived compounds presented by the MHC-like molecule, MR1. These foreign antigens are produced by a wide variety of microbes, including commensal and pathogenic bacteria or yeasts. MAIT cells expend shortly after birth and constitute the major antibacterial T cell subset...
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The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm g...
Data
Tables S1–S6. Description and univariable analyses for all covariates. (DOC)
Data
Tables S7 and S8. Multivariable models for the case-control analysis of risk factors for probable infection in CoPanFlu-France unvaccinated subjects: sensitivity analysis. (DOC)
Article
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Natural killer (NK) cells play a prominent role at the intersection between innate and cognate immunity, thus influencing the development of multiple pathological conditions including HIV-1-induced AIDS. Not only NK cells directly kill HIV-1-infected cells, but also control the maturation and/or elimination of dendritic cells (DCs). These functions...
Article
Dans les pays industrialisés, l’accroissement de l’espérance de vie s’accompagne d’une proportion plus importante de personnes âgées pour lesquelles la prévention, en particulier des infections, est un enjeu majeur de santé publique. La grippe, les infections à pneumocoque, la coqueluche, le zona, le tétanos et dans une moindre mesure, la diphtérie...
Article
In developed countries, the population is getting older and the prevention of infectious diseases is therefore a major public health issue for elderly. Infectious diseases preventable by vaccination, including influenza, pneumococcal infection, pertussis, herpes zoster infections, and to a lesser extent, diphtheria and poliomyelitis, are direct or...
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The risk of influenza infection depends on biological characteristics, individual or collective behaviors and the environmental context. The Cohorts for Pandemic Influenza (CoPanFlu) France study was set up in 2009 after the identification of the novel swine-origin A/H1N1 pandemic influenza virus. This cohort of 601 households (1450 subjects) repre...
Data
Design and methods of the CoPanFlu-France cohort: representativeness of the population sample.
Article
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Background Plasmacytoid dendritic cells (pDCs) mainly contribute to antiviral immunity through recognition of viral components resulting in the production of type-I interferon (IFN), a powerful innate antiviral cytokine. IFN-alpha production by pDCs is promoted by a cross-talk with NK cells, that triggers in return the cytotoxicity of NK cells. Giv...
Article
Monitoring T cells in combination with humoral response may be of value to predict clinical protection and cross-protective immunity after influenza vaccination. Elispot technique which measures cytokine produced after antigen-specific T cell stimulation is used routinely to detect and characterize anti-viral T cells. We found that the preservative...
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Human CD4(+) αβ T cells are activated via T-cell receptor recognition of peptide epitopes presented by major histocompatibility complex (MHC) class II (MHC-II). The open ends of the MHC-II binding groove allow peptide epitopes to extend beyond a central nonamer core region at both the amino- and carboxy-terminus. We have previously found that these...
Article
Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4(+) T cells may persist following viral rebound has not been fully investigated. Patients with CD4(+) T cells 500/μl or more and HIV RNA less than 50 copies/ml were randomized to continue antiretroviral therapy (ART) either alone (n = 67) or combined with three IL-2 cyc...
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Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral...