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450 results on '"Gougeon, Marie lise"'

1. SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Author

Allouch, Awatef, Di Primio, Cristina, Paoletti, Audrey, Lê-Bury, Gabrielle, Subra, Frédéric, Quercioli, Valentina, Nardacci, Roberta, David, Annie, Saïdi, Héla, Cereseto, Anna, Ojcius, David M, Montagnac, Guillaume, Niedergang, Florence, Pancino, Gianfranco, Saez-Cirion, Asier, Piacentini, Mauro, Gougeon, Marie-Lise, Kroemer, Guido, and Perfettini, Jean-Luc

Subjects
HIV/AIDS, Infectious Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Acetylation, Active Transport, Cell Nucleus, Anti-HIV Agents, Cell Cycle Proteins, Drug Resistance, Viral, HIV Infections, HIV-1, Humans, Microtubule-Associated Proteins, Microtubules, Raltegravir Potassium, Virus Replication, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

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 and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.

Published
2020

2. Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling.

Author

Bos, Sandra, Poirier-Beaudouin, Béatrice, Seffer, Valérie, Manich, Maria, Mardi, Cartini, Desprès, Philippe, Gadea, Gilles, and Gougeon, Marie-Lise

Subjects
CD303, IFN—interferon, Zika virus (ZIKV), non-structural protein 1 (NS1), plasmacytoid dendritic cells (pDC), Animals, Cell Line, Chlorocebus aethiops, Cytokines, Dendritic Cells, Down-Regulation, Humans, Inflammation, Interferon-alpha, Lectins, C-Type, Membrane Glycoproteins, Receptors, Immunologic, Signal Transduction, Vero Cells, Zika Virus, Zika Virus Infection
Abstract

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 about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.

Published
2020

4. Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.

Author

Martins, Isabelle, Raza, Syed Qasim, Voisin, Laurent, Dakhli, Haithem, Allouch, Awatef, Law, Frédéric, Sabino, Dora, De Jong, Dorine, Thoreau, Maxime, Mintet, Elodie, Dugué, Delphine, Piacentini, Mauro, Gougeon, Marie-Lise, Jaulin, Fanny, Bertrand, Pascale, Brenner, Catherine, Ojcius, David M, Kroemer, Guido, Modjtahedi, Nazanine, Deutsch, Eric, and Perfettini, Jean-Luc

Subjects
Cell Line, Tumor, HCT116 Cells, Jurkat Cells, Animals, Humans, Mice, Neoplasms, Cisplatin, Paclitaxel, Antineoplastic Agents, Radiotherapy, Bystander Effect, Cell Death, Apoptosis, Gamma Rays, MCF-7 Cells, Oxaliplatin, Cell Line, Tumor, Biochemistry and Cell Biology, Oncology and Carcinogenesis
Abstract

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 with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.

Published
2018

5. Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study

Author

Cohen, Dani, Atsmon, Jacob, Artaud, Cécile, Meron-Sudai, Shiri, Gougeon, Marie-Lise, Bialik, Anya, Goren, Sophy, Asato, Valeria, Ariel-Cohen, Ortal, Reizis, Arava, Dorman, Alexandra, Hoitink, Carla W G, Westdijk, Janny, Ashkenazi, Shai, Sansonetti, Philippe, Mulard, Laurence A, and Phalipon, Armelle

Published
2021
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6. HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry

Author

Paoletti, Audrey, Allouch, Awatef, Caillet, Marina, Saïdi, Hela, Subra, Frédéric, Nardacci, Roberta, Wu, Qiuji, Muradova, Zeinaf, Voisin, Laurent, Raza, Syed Qasim, Law, Frédéric, Thoreau, Maxime, Dakhli, Haithem, Delelis, Olivier, Poirier-Beaudouin, Béatrice, Dereuddre-Bosquet, Nathalie, Le Grand, Roger, Lambotte, Olivier, Saez-Cirion, Asier, Pancino, Gianfranco, Ojcius, David M., Solary, Eric, Deutsch, Eric, Piacentini, Mauro, Gougeon, Marie-Lise, Kroemer, Guido, and Perfettini, Jean-Luc

Published
2019
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7. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial

Author

Tardieu, Marc, Zérah, Michel, Gougeon, Marie-Lise, Ausseil, Jérome, de Bournonville, Stéphanie, Husson, Béatrice, Zafeiriou, Dimitrios, Parenti, Giancarlo, Bourget, Philippe, Poirier, Béatrice, Furlan, Valérie, Artaud, Cécile, Baugnon, Thomas, Roujeau, Thomas, Crystal, Ronald G, Meyer, Christian, Deiva, Kumaran, and Heard, Jean-Michel

Published
2017
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10. Data from Antitumor Immunity Triggered by Melphalan Is Potentiated by Melanoma Cell Surface–Associated Calreticulin

Author

Dudek-Perić, Aleksandra M., primary, Ferreira, Gabriela B., primary, Muchowicz, Angelika, primary, Wouters, Jasper, primary, Prada, Nicole, primary, Martin, Shaun, primary, Kiviluoto, Santeri, primary, Winiarska, Magdalena, primary, Boon, Louis, primary, Mathieu, Chantal, primary, van den Oord, Joost, primary, Stas, Marguerite, primary, Gougeon, Marie-Lise, primary, Golab, Jakub, primary, Garg, Abhishek D., primary, and Agostinis, Patrizia, primary

Published
2023
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11. Supplementary Tables 1-3 from Antitumor Immunity Triggered by Melphalan Is Potentiated by Melanoma Cell Surface–Associated Calreticulin

Author

Dudek-Perić, Aleksandra M., primary, Ferreira, Gabriela B., primary, Muchowicz, Angelika, primary, Wouters, Jasper, primary, Prada, Nicole, primary, Martin, Shaun, primary, Kiviluoto, Santeri, primary, Winiarska, Magdalena, primary, Boon, Louis, primary, Mathieu, Chantal, primary, van den Oord, Joost, primary, Stas, Marguerite, primary, Gougeon, Marie-Lise, primary, Golab, Jakub, primary, Garg, Abhishek D., primary, and Agostinis, Patrizia, primary

Published
2023
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12. Supplementary materials and methods from Antitumor Immunity Triggered by Melphalan Is Potentiated by Melanoma Cell Surface–Associated Calreticulin

Author

Dudek-Perić, Aleksandra M., primary, Ferreira, Gabriela B., primary, Muchowicz, Angelika, primary, Wouters, Jasper, primary, Prada, Nicole, primary, Martin, Shaun, primary, Kiviluoto, Santeri, primary, Winiarska, Magdalena, primary, Boon, Louis, primary, Mathieu, Chantal, primary, van den Oord, Joost, primary, Stas, Marguerite, primary, Gougeon, Marie-Lise, primary, Golab, Jakub, primary, Garg, Abhishek D., primary, and Agostinis, Patrizia, primary

Published
2023
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13. Supplementary Figures 1-6 from Antitumor Immunity Triggered by Melphalan Is Potentiated by Melanoma Cell Surface–Associated Calreticulin

Author

Dudek-Perić, Aleksandra M., primary, Ferreira, Gabriela B., primary, Muchowicz, Angelika, primary, Wouters, Jasper, primary, Prada, Nicole, primary, Martin, Shaun, primary, Kiviluoto, Santeri, primary, Winiarska, Magdalena, primary, Boon, Louis, primary, Mathieu, Chantal, primary, van den Oord, Joost, primary, Stas, Marguerite, primary, Gougeon, Marie-Lise, primary, Golab, Jakub, primary, Garg, Abhishek D., primary, and Agostinis, Patrizia, primary

Published
2023
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14. Human papilloma virus‐16‐specific CD8+ T‐cell expansions characterize different clinical forms of lichen planus and not lichen sclerosus et atrophicus

Author

Viguier, Manuelle, primary, Pérals, Corine, additional, Poirier, Béatrice, additional, Battistella, Maxime, additional, Aubin, François, additional, Bachelez, Hervé, additional, Prétet, Jean‐Luc, additional, Gheit, Tarik, additional, Tommasino, Massimo, additional, Touzé, Antoine, additional, Gougeon, Marie‐Lise, additional, and Fazilleau, Nicolas, additional

Published
2023
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16. Causal analysis of H1N1pdm09 influenza infection risk in a household cohort

Author

Mansiaux, Yohann, Salez, Nicolas, Lapidus, Nathanael, Setbon, Michel, Andreoletti, Laurent, Leruez-Ville, Marianne, Cauchemez, Simon, Gougeon, Marie-Lise, Vély, Frédéric, Schwarzinger, Michael, Abel, Laurent, Delabre, Rosemary Markovic, Flahault, Antoine, de Lamballerie, Xavier, and Carrat, Fabrice

Published
2015

24. Intracerebral Gene Therapy in Four Children with Sanfilippo B Syndrome: 5.5-Year Follow-Up Results

Author

Deiva, Kumaran, primary, Ausseil, Jérôme, additional, de Bournonville, Stéphanie, additional, Zérah, Michel, additional, Husson, Béatrice, additional, Gougeon, Marie-Lise, additional, Poirier-Beaudouin, Béatrice, additional, Zafeiriou, Dimitrios, additional, Parenti, Giancarlo, additional, Heard, Jean-Michel, additional, and Tardieu, Marc, additional

Published
2021
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27. Safety and immunogenicity of SC599, an oral live attenuated Shigella dysenteriae type-1 vaccine in healthy volunteers: Results of a Phase 2, randomized, double-blind placebo-controlled trial

Author

Launay, Odile, Sadorge, Christine, Jolly, Nathalie, Poirier, Béatrice, Béchet, Stéphane, van der Vliet, Diane, Seffer, Valérie, Fenner, Nicola, Dowling, Kelly, Giemza, Raphaela, Johnson, Julie, Ndiaye, Anna, Vray, Muriel, Sansonetti, Philippe, Morand, Philippe, Poyart, Claire, Lewis, David, and Gougeon, Marie-Lise

Published
2009
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28. Cell-mediated immunity to NAGLU transgene following intracerebral gene therapy in children with Mucopolysaccharidosis type IIIB syndrome

Author

Gougeon, Marie-Lise, Poirier-Beaudouin, Béatrice, Ausseil, Jérome, Zérah, Michel, Artaud, Cécile, Heard, Jean-Michel, Deiva, Kumaran, Tardieu, Marc, Département Infection et Epidémiologie - Department of Infection and Epidemiology, Institut Pasteur [Paris], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Biothérapies pour les Maladies Neurodégénératives, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Neurologie Pédiatrique [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut Pasteur sponsored the study during thefirst 30 monthsand UniQure sponsored it for the following 36 months. Thestudy was supported by funds from the'Association FrançaiseContre les Myopathies (AFM)', the patients‘association'Vaincreles Maladies Lysosomales', the Institut Pasteur, the Conny MaevaCharitable Foundation, and a gift from the Akbaraly family., Institut Pasteur [Paris] (IP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, and Institut Pasteur sponsored the study during thefirst 30 monthsand UniQure sponsored it for the following 36 months. Thestudy was supported by funds from the'Association Française Contre les Myopathies (AFM)', the patients‘association'Vaincreles Maladies Lysosomales', the Institut Pasteur, the Conny MaevaCharitable Foundation, and a gift from the Akbaraly family.

Subjects
NAGLU, T-Lymphocytes, [SDV]Life Sciences [q-bio], Genetic Vectors, Immunology, MESH: Mucopolysaccharidosis III / complications, T cells, cellular immunity, Lymphocyte Activation, MESH: Immunity, Cellular, MESH: Acetylglucosaminidase / genetics, MESH: Genetic Therapy / adverse effects, Mucopolysaccharidosis III, MESH: Mucopolysaccharidosis III / genetics, MESH: Child, Acetylglucosaminidase, MESH: Acetylglucosaminidase / immunology, Humans, Transgenes, MESH: Lymphocyte Activation, Child, Original Research, Immunity, Cellular, Drug Administration Routes, MESH: Cytokines / metabolism, MESH: Genetic Therapy / methods, MESH: Genetic Vectors / administration & dosage, AAV, Genetic Therapy, RC581-607, cytokines, MESH: Drug Administration Routes, MESH: Genetic Vectors / genetics, MESH: Immunologic Memory, MPS IIIB, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic diseases. Allergy, CNS, Immunologic Memory
Abstract

International audience; 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 human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. It was reported that AAV-mediated gene therapies might elicit a strong host immune response resulting in decreased transgene expression. To address this issue, we performed a comprehensive analysis of cellular immunity and cytokine patterns generated against the therapeutic enzyme in the four treated children over 5.5 years of follow-up. We report the emergence of memory and polyfunctional CD4+ and CD8+ T lymphocytes sensitized to the transgene soon after the start of therapy, and appearing in peripheral blood in waves throughout the follow-up. However, this response had no apparent impact on CNS transgene expression, which remained stable 66 months after surgery, possibly a consequence of the long-term immunosuppressive treatment. We also report that gene therapy did not trigger neuroinflammation, evaluated through the expression of cytokines and chemokines in patients' CSF. Milder disease progression in the youngest patient was found associated with low level and less differentiated circulating NAGLU-specific T cells, together with the lack of proinflammatory cytokines in the CSF. Findings in this study support a systematic and comprehensive immunomonitoring approach for understanding the impact immune reactions might have on treatment safety and efficacy of gene therapies.

Published
2021
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36. A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome

Author

Marrella, Veronica, Poliani, Pietro Luigi, Casati, Anna, Rucci, Francesca, Frascoli, Laura, Gougeon, Marie-Lise, Lemercier, Brigitte, Bosticardo, Marita, Ravanini, Maria, Battaglia, Manuela, Roncarolo, Maria Grazia, Cavazzana-Calvo, Marina, Facchetti, Fabio, Notarangelo, Luigi D., Vezzoni, Paolo, Grassi, Fabio, and Villa, Anna

Subjects
Immunodeficiency -- Research, Immunodeficiency -- Care and treatment, Immunodeficiency -- Analysis
Abstract

Rag enzymes are the main players in V(D)J recombination, the process responsible for rearrangement of TCR and Ig genes. Hypomorphic Rag mutations in humans, which maintain partial V(D)J activity, cause [...]

Published
2007

41. Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity

Author

Lagresle-Peyrou, Chantal, Yates, Frank, Malassis-Séris, Michèle, Hue, Christophe, Morillon, Estelle, Garrigue, Alexandrine, Liu, Allen, Hajdari, Philippe, Stockholm, Daniel, Danos, Olivier, Lemercier, Brigitte, Gougeon, Marie-Lise, Rieux-Laucat, Frederic, de Villartay, Jean-Pierre, Fischer, Alain, and Cavazzana-Calvo, Marina

Published
2006
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43. Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV

Author

Lévy, Yves, Thiébaut, Rodolphe, Gougeon, Marie-Lise, Molina, Jean-Michel, Weiss, Laurence, Girard, Pierre-Marie, Venet, Alain, Morlat, Philippe, Poirier, Béatrice, Lascaux, Anne-Sophie, Boucherie, Céline, Sereni, Daniel, Rouzioux, Christine, Viard, Jean-Paul, Lane, Cliff, Delfraissy, Jean-François, Sereti, Irini, and Chêne, Geneviève

Published
2012
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44. Association between pandemic and seasonal influenza vaccination and haemagglutination antibody titers against A/H1N1v: a national representative survey in France, nested in the “Cohorts for Pandemic Influenza” (CoPanFlu - France)

Author

Lapidus, Nathanaël, de Lamballerie, Xavier, Salez, Nicolas, Moyen, Nanikaly, Ferrari, Pascal, Gougeon, Marie-Lise, Vely, Frédéric, Leruez-Ville, Marianne, Andreoletti, Laurent, Cauchemez, Simon, Boëlle, Pierre-Yves, Vivier, Eric, Abel, Laurent, Schwarzinger, Michaël, Setbon, Michel, Legeas, Michèle, Le Cann, Pierre, Flahault, Antoine, and Carrat, Fabrice

Published
2011

48. A Single Cycle of Rituximab for the Treatment of Severe Pemphigus

Author

Joly, Pascal, Mouquet, Hugo, Roujeau, Jean-Claude, D'Incan, Michel, Gilbert, Daniele, Jacquot, Serge, Gougeon, Marie-Lise, Bedane, Christophe, Muller, Ralf, Dreno, Brigitte, Doutre, Marie-Sylvie, Delaporte, Emmanuel, Pauwels, Christine, Franck, Nathalie, Caux, Frederic, Picard, Catherine, Tancrede-Bohin, Emmanuelle, Bernard, Philippe, Tron, Francois, Hertl, Michael, and Musette, Philippe.

Published
2007
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50. Induction of 'tissue' transglutaminase in HIV pathogenesis: evidence for high rate of apoptosis of CD4+ T lymphocytes and accessory cells in lymphoid tissues

Author

Amendola, Alessandra, Gougeon, Marie-Lise, Poccia, Fabrizio, Bondurand, Alain, Fesus, Laszlo, and Piacentini, Mauro

Subjects
Transglutaminases -- Research, HIV (Viruses) -- Research, Lymphoid tissue -- Research, Cell death -- Research, Science and technology
Abstract

Peripheral blood mononuclear cells and lymphoid tissues from HIV-infected individuals display high levels of 'tissue' transglutaminase (tTG) with respect to seronegative persons. In asymptomatic individuals, [greater than]80% of the circulating CD[4.sup.+] T cells synthesize tTG protein and the number of these cells matches the level of apoptosis detected in the peripheral blood mononuclear cells from the same patients. In HIV-infected lymph nodes tTG protein is localized in large number of cells (macrophages, follicular dendritic cells, and endothelial cells), showing distinctive morphological and biochemical features of apoptosis as well as in lymphocytes and syncytia. These findings demonstrate that during the course of HIV infection, high levels of apoptosis also occur in the accessory cells of lymphoid organs. The increased concentration of [Epsilon]([Gamma]-glutamyl)lysine isodipeptide, the degradation product of tTG cross-linked proteins, observed in the blood of HIV-infected individuals demonstrates that the enzyme accumulated in the dying cells actively cross-links intracellular proteins. The enhanced levels of [Epsilon]([Gamma]-glutamyl)lysine in the blood parallels the progression of HIV disease, suggesting that the isodipeptide determination might be a useful method to monitor the in vivo rate of apoptosis.

Published
1996

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