Search

Your search keyword '"Fahd Benjelloun"' showing total 11 results
Start Over Author "Fahd Benjelloun"
11 results on '"Fahd Benjelloun"'

1. Activation of Toll-Like Receptors Differentially Modulates Inflammation in the Human Reproductive Tract: Preliminary Findings

Author

Fahd Benjelloun, Héloïse Quillay, Claude Cannou, Romain Marlin, Yoann Madec, Hervé Fernandez, Fabrice Chrétien, Roger Le Grand, Françoise Barré-Sinoussi, Marie-Thérèse Nugeyre, and Elisabeth Menu

Subjects
female reproductive tract (FRT), Toll-like receptors (TLR), cytokines and chemokines, immune cells, mucosa, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract

The female reproductive tract (FRT) is the main site of entry of sexually transmitted infections (STIs). Toll-like receptors (TLRs) that recognize pathogenic motifs are widely expressed in the FRT. TLR stimulation induces immune activation and local production of inflammatory mediators. In the FRT, this response should also be compatible with reproductive functions and symbiosis with host microbiota. With a view to develop efficient mucosal vaccines to prevent STI acquisition, the role of TLR ligands in the FRT needs to be explored. We have therefore investigated the cytokine profiles of the different compartments of the FRT (vagina, endocervix, ectocervix, and uterus) before and after stimulation of mononuclear cells from human tissue specimens. The comparison with PBMCs allowed us to highlight the FRT specificities. We first characterized the main immune cell populations in each compartment and observed that their distribution was different through the compartments. The CD45+ cells represented a maximum of 11% in the FRT in contrast to 96% in PBMCs. We identified two main populations among the CD45+ cells in the four compartments of the FRT: CD3+ T cells (CD4+ and CD8+) and CD14+ APCs. B cell populations (CD19+) were much less frequent than T cells in all the FRT regions and were equally distributed. NK CD56+ cells were detected in all compartments and were more abundant in the uterus. Stimulation of the mononuclear cells was then performed with TLR agonists: R848 for TLR7/8, Poly I:C for TLR3, LPS for TLR4 and ODN CpG for TLR9. Cytokine levels in unstimulated cultures of cells isolated from all FRT compartments were higher than in cultures of unstimulated PBMCs. In contrast, after stimulation with TLR agonists, cytokine responses induced by TLR agonists were moderate in the FRT and significantly lower than in PBMCs. These responses were varied with different TLR ligands and FRT compartments. The cytokine profile induced by TLR activation in the FRT supports the role of these tissues in genital anti-microbial immunity and in the control of inflammation while allowing maintenance of its reproductive function.

Published
2020
Full Text
View/download PDF

2. Dynamics of Vaginal and Rectal Microbiota Over Several Menstrual Cycles in Female Cynomolgus Macaques

Author

Marie-Thérèse Nugeyre, Nicolas Tchitchek, Cindy Adapen, Claude Cannou, Vanessa Contreras, Fahd Benjelloun, Jacques Ravel, Roger Le Grand, Romain Marlin, and Elisabeth Menu

Subjects
cynomolgus macaques, female hormones, microbiota, mucosa, rectum, vagina, Microbiology, QR1-502
Abstract

The composition of the microbiota in cynomolgus macaques is only partially characterized, although this animal model is often used to study pathogenesis and preventive strategies against infections. We thus performed, for the first time, a longitudinal characterization of the vaginal and rectal microbiota of five cycling female cynomolgus macaques. Samples were collected weekly for 15 weeks and the V3/V4 regions of the16S rRNA gene sequenced. Sequences were analyzed with QIIME for OTU detection and taxonomic assignment. Progesterone levels were also determined to evaluate hormonal influence on bacteria relative abundance. The rectal and vaginal bacterial composition in cynomolgus macaques is polymicrobial and clearly distinct, with larger individual variability in the vagina. Rectal microbiota profiles were consistent between animals, whereas they were highly variable and animal-specific in the vagina. In the rectum, the most abundant taxa were Ruminococcaceae, Prevotella, and Clostridiales. In the vagina, the most abundant genera were Sneathia, Porphyromonas, Prevotella, and Fusobacterium. Lactobacillus were found at relative abundances higher than 1% in only one animal and were not predominant. Comparison of the vaginal cynomolgus macaque microbiota with that of humans showed similarity to community state type IV-A usually associated with dysbiosis. In the vagina, the relative abundance of 12 bacterial genera was found to be associated with progesterone levels. Our study provides a detailed characterization of the rectal and vaginal microbiota in female cynomolgus macaques and opens new perspectives of this animal model.

Published
2019
Full Text
View/download PDF

3. Seminal Plasma Exposures Strengthen Vaccine Responses in the Female Reproductive Tract Mucosae

Author

Romain Marlin, Marie-Thérèse Nugeyre, Nicolas Tchitchek, Matteo Parenti, Cécile Lefebvre, Hakim Hocini, Fahd Benjelloun, Claude Cannou, Silvia Nozza, Nathalie Dereuddre-Bosquet, Yves Levy, Françoise Barré-Sinoussi, Gabriella Scarlatti, Roger Le Grand, and Elisabeth Menu

Subjects
female reproductive tract (FRT), seminal plasma, vaccine, mucosa, HIV-1, Immunologic diseases. Allergy, RC581-607
Abstract

HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells, and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.

Published
2019
Full Text
View/download PDF

4. A high mucosal blocking score is associated with HIV protection

Author

Mario Clerici, Bernard Verrier, Norma Rallón, Blandine Chanut, Jorge del Romero, Alexandre Girard, Christian Genin, Stéphane Paul, Mara Biasin, Frédéric Lucht, Fabienne Jospin, José M. Benito, Jean Jacques Pin, Fahd Benjelloun, Carmen Rodríguez, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Universidad Autonoma de Madrid (UAM), Institut Pasteur [Paris], Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service d'immunologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, A.G. was supported by a doctoral fellowship from Region Rhone-Alpes (France). This work was financed by research grants from Region Rhone-Alpes, ANRS, and Sidaction., Université Jean Monnet - Saint-Étienne (UJM), Universidad Autónoma de Madrid (UAM), Institut Pasteur [Paris] (IP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie - Suivi des biothérapies [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Università degli Studi di Milano = University of Milan (UNIMI), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Centre International de Recherche en Infectiologie (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Integrins, MESH: HIV Antibodies/immunology, Human immunodeficiency virus (HIV), HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, medicine.disease_cause, highly exposed seronegative, Cohort Studies, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, 030212 general & internal medicine, Receptor, MESH: Cohort Studies, biology, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, MESH: Immunity, Mucosal, Protein Binding, Adult, Langerin, Immunology, Virus Attachment, Receptors, Cell Surface, DC-SIGN, MESH: Antigens, CD/metabolism, 03 medical and health sciences, MESH: HIV Envelope Protein gp120/metabolism, Antigen, Antigens, CD, Immunity, medicine, Humans, Lectins, C-Type, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Immunity, Mucosal, MESH: Cell Adhesion Molecules/metabolism, MESH: Humans, business.industry, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, mucosal blocking score, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, gp120, Mannose-Binding Lectins, 030104 developmental biology, [CHIM.POLY]Chemical Sciences/Polymers, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, langerin, biology.protein, MESH: HIV Infections/immunology, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, Cell Adhesion Molecules, MESH: Female
Abstract

International audience; BACKGROUND:Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as α4β7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN).METHOD:Here, we studied gp120-specific antibodies ability to block HIV interaction with α4β7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to α4β7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/α4β7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV+ patients or HIV- unexposed healthy individuals.RESULTS:Antibodies reducing gp120 binding to both α4β7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV+ patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of α4β7 CD4+ T cells with primary isolates.CONCLUSIONS:MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues.

Published
2019
Full Text
View/download PDF

5. Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry

Author

Elisabeth Menu, Nathalie Dereuddre-Bosquet, Claude Cannou, Roger Le Grand, Matteo Parenti, Hakim Hocini, Marie-Thérèse Nugeyre, Françoise Barré-Sinoussi, Romain Marlin, Nicolas Tchitchek, Fahd Benjelloun, Yves Levy, Gabriella Scarlatti, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-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), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Direction Internationale de l'Institut Pasteur, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, This work was supported by the French Government Programme d’Investissements d’Avenir (Grant ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies infrastructure and Grants ANR-10-LABX-77 and ANR-10-EQPX-02-01 funding the Vaccine Research Institute and the FlowCyTech facility, respectively)., We thank Dr. Anne-Sophie Beignon, Dr. Antonio Cosma, Dr. Mireille Centlivre, and the B Cell and Mucosae division members for scientific discussions, D. Young for critical editing of the manuscript, Transgene for providing the wt MVA strain, l'Agence nationale de recherche sur le sida et les hépatites virales /INSERM and the Vaccine Research Institute for providing the MVA–HIV-B vaccine, the Infectious Disease Models and Innovative Therapies Core Facilities for animal intervention and sampling, Rahima Yousfi for technical assistance, and Dr. Bernard Verrier for providing the p24 HIV-1 Ag., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), Vaccine Research Institute (VRI), Bidault, Floran, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, and Equipements d'excellence - Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales - - FlowCyTech2010 - ANR-10-EQPX-0002 - EQPX - VALID

Subjects
0301 basic medicine, T-Lymphocytes, viruses, [SDV]Life Sciences [q-bio], Uterus, Antibodies, Viral, Reproductive Tract Infections, chemistry.chemical_compound, Vaccinia, Immunology and Allergy, Antigens, Viral, Cells, Cultured, AIDS Vaccines, Immunity, Cellular, Vaccination, Innate lymphoid cell, Genitalia, Female, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Primates, endocrine system, Genetic Vectors, Immunology, Antigen-Presenting Cells, Vaccinia virus, Biology, Virus, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Immune system, Disease Transmission, Infectious, medicine, Animals, Humans, Cervix, Viral Vaccines, Virology, Immunity, Humoral, Immunoglobulin A, 030104 developmental biology, chemistry, Immunoglobulin G, HIV-1, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Immunologic Memory, CD8
Abstract

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.

Published
2017
Full Text
View/download PDF

6. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations

Author

Alexandre Girard, Fabienne Jospin, Christian Genin, Gaël Champier, Bernard Verrier, Stéphane Paul, Michel Cogné, Nicole M. Thielens, Blandine Chanut, Nicolas Rochereau, Zeliha Oruc, Nadine Vincent, Fahd Benjelloun, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, B-Cell Design (B-Cell Design), Groupe d'Immunité des Muqueuses et Agents Pathogènes, Université de Lyon, Université Jean Monnet - Saint-Étienne (UJM), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Immunoglobulin A, Saliva, Somatic cell, viruses, Immunology, Fluorescent Antibody Technique, Mice, Transgenic, HIV Antibodies, Gp41, Epitope, Epitopes, Mice, 03 medical and health sciences, Animals, Immunology and Allergy, Mucous Membrane, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Antibodies, Monoclonal, virus diseases, Antibodies, Neutralizing, Virology, HIV Envelope Protein gp41, Recombinant Proteins, 3. Good health, 030104 developmental biology, Transcytosis, Mutation, Monoclonal, HIV-1, biology.protein, Viral load
Abstract

Mucosal HIV-1–specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir.

Published
2016
Full Text
View/download PDF

7. The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication

Author

Héloïse Quillay, H. El Costa, Marion Duriez, J Ighil, Romain Marlin, Françoise Barré-Sinoussi, Fahd Benjelloun, C. de Truchis, Elisabeth Menu, Claude Cannou, M. Rahmati, Marie-Thérèse Nugeyre, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by ANRS (HEC and HQfinancial support and grant #12165/13129), Sidaction (HEC and MD financial support and grant# AI20-3-01671), the TOTAL Foundation, INSERM, and Institut Pasteur, Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and MENU, Elisabeth

Subjects
Cyclin-Dependent Kinase Inhibitor p21, 0301 basic medicine, Cellular differentiation, Immunology, HIV Infections, Biology, Virus Replication, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Interferon, Decidua, medicine, Humans, Immunology and Allergy, Macrophage, Interferon gamma, Receptor, Immunity, Mucosal, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cells, Cultured, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Macrophages, Cell Differentiation, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Cellular Microenvironment, Toll-Like Receptor 7, Viral replication, Toll-Like Receptor 8, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Female, Ex vivo, 030215 immunology, medicine.drug
Abstract

International audience; Macrophages from the decidua basalis (dM), the main uterine mucosa during pregnancy, are weakly permissive to HIV-1 infection. Here, we investigated the mechanisms underlying this natural control. We show, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences dM differentiation and naturally protects these cells from HIV-1 infection. Interferon (IFN)-γ, present in the decidual tissue, contributes to maintenance of the dM phenotype and restricts HIV-1 infection by mechanisms involving the cyclin-dependent kinase inhibitor p21Cip1/Waf1. We also found that activation of Toll-like receptors 7 and 8 expressed by dM reinforces the low permissivity of dM to HIV-1 by restricting viral replication and inducing secretion of cytokines in the decidual environment, including IFN-γ, that shape dM plasticity. A major challenge for HIV-1 eradication is to control infection of tissue-resident macrophages in the female reproductive tract. Our findings provide clues to the development of novel strategies to prevent HIV-1 macrophage infection.

Published
2016
Full Text
View/download PDF

8. Role of human immunodeficiency virus type 1 envelope structure in the induction of broadly neutralizing antibodies

Author

Christian Genin, Bernard Verrier, P. Lawrence, Stéphane Paul, and Fahd Benjelloun

Subjects
biology, Immunology, Human immunodeficiency virus (HIV), Viremia, HIV Antibodies, medicine.disease, medicine.disease_cause, Microbiology, Virology, Antibodies, Neutralizing, Neutralization, Viral Envelope Proteins, Insect Science, biology.protein, medicine, HIV-1, Minireview, Antibody, Elite controllers
Abstract

Very soon after the discovery of neutralizing antibodies (NAbs) toward human immunodeficiency virus type 1 (HIV-1) infection, it became apparent that characterization of these NAbs would be an important step in finding a cure for or a vaccine to eradicate HIV-1. Since the initial description of broadly cross-clade NAbs naturally produced in HIV-1 patients, numerous studies have described new viral targets for these antibodies. More recently, studies concerning new groups of patients able to control their viremia, such as long-term nonprogressors (LTNPs) or elite controllers, have described the generation of numerous envelope-targeted NAbs. Recent studies have marked a new stage in research on NAbs with the description of antibodies obtained from a worldwide screening of HIV-positive patients. These studies have permitted the discovery of NAb families with great potential for both neutralization and neutralization breadth, such as PG, PGT, CH, and highly active agonistic anti-CD4 binding site antibodies (HAADs), of which VRC01 and its variants are members. These antibodies are able to neutralize more than 80% of circulating strains without any autoreactivity and can be rapidly integrated into clinical trials in order to test their protective potential. In this review, we will focus on new insights into HIV-1 envelope structure and their implications for the generation of potent NAbs.

Published
2012

9. HIV-1 Glycoprotein Immunogenicity

Author

Stéphane Paul, Fahd Benjelloun, and Christian Genin

Subjects
biology, viruses, RNA, Viral membrane, biology.organism_classification, Virology, Virus, Reverse transcriptase, chemistry.chemical_compound, Retrovirus, chemistry, MHC class I, biology.protein, Polymerase, DNA
Abstract

The Human Immunodeficiency Virus type 1 (HIV-1) is a C-type enveloped retrovirus (classification based on morphology of retroviruses electron microscopy) of the Retroviridae family. It’s consisting in a genome of 2 positive stranded RNA molecules and a specific polymerase reverse transcriptase enzyme (RT). The viral RNA is reverse transcribed by RT into a double-stranded DNA molecule which is then integrated into the genome of infected cells (figure 1). The virus is wrapped by a bilayer membrane derived from the host cell. Homotrimers of the viral glycoprotein gp160 are inserted in the envelope (figure 1). Several cellular proteins are also incorporated into the viral membrane with relative abundance, including MHC class I and II molecules and intracellular adhesion molecule. Lentiviruses, to which HIV belongs, cause disease with a 'slow' evolution preceded by a period of clinical latency. Apart from humans, lentiviruses infect several other species of mammals such as

Published
2011
Full Text
View/download PDF

11. Promyelocytic leukemia-nuclear body formation is an early event leading to retinoic acid-induced differentiation of neuroblastoma cells

Author

Camille Ripoll, Fahd Benjelloun, A. Delaune, E. Legrand, Cécile Corbière, Vannier Jp, Marc Vasse, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), and Université de Rouen Normandie (UNIROUEN)

Subjects
MESH: Neoplasm Proteins, MESH: Signal Transduction, MAPK/ERK pathway, [SDV]Life Sciences [q-bio], viruses, Cellular differentiation, Retinoic acid, Promyelocytic Leukemia Protein, Biochemistry, Neuroblastoma, chemistry.chemical_compound, 0302 clinical medicine, MESH: Promyelocytic Leukemia Protein, Enzyme Inhibitors, Phosphorylation, Nuclear protein, Extracellular Signal-Regulated MAP Kinases, MESH: Extracellular Signal-Regulated MAP Kinases, 0303 health sciences, Nuclear Proteins, virus diseases, Cell Differentiation, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, Neoplasm Proteins, 3. Good health, Gene Expression Regulation, Neoplastic, MESH: Enzyme Inhibitors, 030220 oncology & carcinogenesis, [SDE]Environmental Sciences, Signal transduction, Signal Transduction, medicine.drug, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Cell Line, Tumor, education, Tretinoin, Biology, Models, Biological, 03 medical and health sciences, Cellular and Molecular Neuroscience, Promyelocytic leukemia protein, Keratolytic Agents, MESH: Keratolytic Agents, Cell Line, Tumor, MESH: Cell Proliferation, Internal medicine, medicine, Humans, MESH: Tumor Suppressor Proteins, MESH: Cell Nucleus Structures, Cell Proliferation, 030304 developmental biology, MESH: Tretinoin, MESH: Humans, MESH: Phosphorylation, Tumor Suppressor Proteins, MESH: Models, Biological, medicine.disease, MESH: Neuroblastoma, Cell Nucleus Structures, Endocrinology, chemistry, Cancer research, biology.protein, MESH: Nuclear Proteins, Transcription Factors
Abstract

International audience; Neuroblastoma is one of the most common cancers in children. Neuroblastoma differentiation is linked to the presence of the promyelocytic leukemia (PML) protein. Retinoic acid, a powerful differentiation-inducer in vitro, is a potent agent for the treatment of neuroblastoma. Using two different human neuroblastoma cell lines, SH-SY5Y and LA-N-5, we show here that PML protein leads to the formation of nuclear bodies (PML-NB) after only 1 h of retinoic acid treatment and that this formation is mediated by the extracellular signal-regulated kinase (ERK) pathway. Inhibition of protein kinase C also leads to formation of PML-NB via the ERK pathway. Both sumoylation and phosphorylation of PML in an ERK-dependent pathway are also required for formation of PML-NB. Finally, we show that PML-NB formation in neuroblastoma cells is associated with neurite outgrowth. These results support the proposal that the formation of PML-NB is correlated with the differentiation of neuroblastoma cells.

Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results