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5 results on '"Alexandre Giraud"'

1. Alive pathogenic and saprophytic leptospires enter and exit human and mouse macrophages with no intracellular replication

Author

Ignacio Santecchia, Delphine Bonhomme, Stylianos Papadopoulos, Pedro Escoll, Alexandre Giraud-Gatineau, Maryse Moya-Nilges, Frédérique Vernel-Pauillac, Ivo Gomperts Boneca, Catherine Werts, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Spirochètes / Biology of Spirochetes, Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), This work was founded by Institut Pasteur grants PTR2017-66 to CW and PTR2019-310 to Nadia Benaroudj (Institut Pasteur, Unité de Biologie des Spirochètes) for AGG salary. IS has been part of the Pasteur-Paris University (PPU) International PhD program. This program has received funding from the Institut Carnot Pasteur Microbes & Santé, and the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 665807. IS has additionally benefited from a scholarship 'Fin de thèse de science' number FDT201805005258 granted by 'Fondation pour la recherche médicale (FRM).' This work was supported by Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) to IB., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015)

Subjects
Leptospira, Microbiology (medical), Macrophages, Immunology, THP1 cell line, high content confocal microscopy, Leptospira biflexa, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Rats, Gentamicin assay, Mice, Inbred C57BL, Mice, Infectious Diseases, Animals, Humans, Cattle, Leptospirosis, RAW 246.7 cells, Leptospira interrogans, TLRs, intracellularity
Abstract

Leptospira interrogansare pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million peopleperyear worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore considered as sensitive to leptospirosis. In contrast, mice and rats remain asymptomatic upon infection, although they get chronically colonized in their kidneys. Upon infection, leptospires are stealth pathogens that partially escape the recognition by the host innate immune system. Although leptospires are mainly extracellular bacteria, it was suggested that they could also replicate within macrophages. However, contradictory data in the current literature led us to reevaluate these findings. Using a gentamicin–protection assay coupled to high-content (HC) microscopy, we observed that leptospires were internalizedin vivoupon peritoneal infection of C57BL/6J mice. Additionally, three different serotypes of pathogenicL. interrogansand the saprophyticL. biflexaactively infected both human (PMA differentiated) THP1 and mouse RAW264.7 macrophage cell lines. Next, we assessed the intracellular fate of leptospires using bioluminescent strains, and we observed a drastic reduction in the leptospiral intracellular load between 3 h and 6 h post-infection, suggesting that leptospires do not replicate within these cells. Surprisingly, the classical macrophage microbicidal mechanisms (phagocytosis, autophagy, TLR–mediated ROS, and RNS production) were not responsible for the observed decrease. Finally, we demonstrated that the reduction in the intracellular load was associated with an increase of the bacteria in the supernatant, suggesting that leptospires exit both human and murine macrophages. Overall, our study reevaluated the intracellular fate of leptospires and favors an active entrance followed by a rapid exit, suggesting that leptospires do not have an intracellular lifestyle in macrophages.

Published
2022
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2. The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Author

Alexandre Giraud-Gatineau, Brigitte Gicquel, Juan Manuel Coya, Roland Brosch, Gerald Larrouy-Maumus, Elliott M. Bernard, Alexandra Maure, Anne Biton, Michael Thomson, Jade Marrec, Ludovic Tailleux, Maximiliano G. Gutierrez, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Institut Pasteur [Paris] (IP)-Sorbonne Université (SU), Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Medical Research Council Centre for Molecular Bacteriology and Infection [Londres, Royaume-Uni] (MRC CMBI), Imperial College London, Host-Pathogen Interactions in Tuberculosis Laboratory [London], The Francis Crick Institute [London], Shenzhen Nanshan Center for Chronic Disease Control [Shenzhen, China] (ShenZhenCDC), European Commission (604237) (Brigitte Gicquel), Institut Pasteur (Roland Brosch, Brigitte Gicquel, Ludovic Tailleux), Francis Crick Institute (Maximiliano G Gutierrez), Cancer Research UK (FC001092) (Maximiliano G Gutierrez), Medical Research Council (FC001092) (Maximiliano G Gutierrez), Wellcome (FC001092) (Maximiliano G Gutierrez), Engineering and Physical Sciences Research Council (EP/M027007/1) (Gérald Larrouy-Maumus), Fondation pour la Recherche Médicale (FDM201806006250) (Alexandra Maure), Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID) (Roland Brosch), We thank Olivier Neyrolles and Howard E Takiff for reading the manuscript and helpful discussion. We gratefully acknowledge the UTechS Cytometry and Biomarkers and the UTechS Photonic BioImaging (Imagopole) Citech of Institut Pasteur (Paris, France) as well as the France–BioImaging infrastructure network supported by the French National Research Agency (ANR-10–INSB–04, Investments for the Future) for support in conducting this study, in particular PH. Commere for help with flow cytometry. We also thank Charles Privé (CHU Sainte-Justine Integrated Centre for Pediatric Clinical Genomics, Montreal, Canada) and Mickael Orgeur (Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur) for their technical support., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 604237,EC:FP7:NMP,FP7-NMP-2013-LARGE-7,NAREB(2014), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Sorbonne Université (SU), and Institut Pasteur [Paris]

Subjects
[SDV]Life Sciences [q-bio], Antibiotics, host-pathogen interaction, 0601 Biochemistry and Cell Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, antibiotics, immunology, chemistry.chemical_compound, 0302 clinical medicine, Immunology and Inflammation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biology (General), Diarylquinolines, innate immunity, 0303 health sciences, Microbiology and Infectious Disease, Phagocytes, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, General Neuroscience, General Medicine, 3. Good health, Anti-Bacterial Agents, macrophages, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, tuberculosis, Host-Pathogen Interactions, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Research Article, Modern medicine, Tuberculosis, QH301-705.5, medicine.drug_class, Science, Host–pathogen interaction, infectious disease, Biology, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, Immune system, Immunity, medicine, Autophagy, Humans, Calcium Signaling, human, 030304 developmental biology, Innate immune system, General Immunology and Microbiology, microbiology, Mycobacterium tuberculosis, Macrophage Activation, medicine.disease, Immunity, Innate, HEK293 Cells, chemistry, inflammation, Other, Bedaquiline, Lysosomes, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections., eLife digest The discovery of antibiotic drugs, which treat diseases caused by bacteria, has been a hugely valuable advance in modern medicine. They work by targeting specific cellular processes in bacteria, ultimately stopping them from multiplying or killing them outright. Antibiotics sometimes also affect their human hosts and can cause side-effects, such as gut problems or skin reactions. Recent evidence suggests that antibiotics also have an impact on the human immune system. This may happen either indirectly, by affecting ‘friendly’ bacteria normally present in the body, or through direct effects on immune cells. In turn, this could change the effectiveness of drug treatments. For example, if an antibiotic weakens immune cells, the body could have difficulty fighting off the existing infection – or become more vulnerable to new ones. However, even though new drugs are being introduced to combat the worldwide rise of antibiotic-resistant bacteria, their effects on immunity are still not well understood. For example, bedaquiline is an antibiotic recently developed to treat tuberculosis infections that are resistant to several drugs. Giraud-Gatineau et al. wanted to determine if bedaquiline altered the human immune response to bacterial infection independently from its direct anti-microbial effects. Macrophages engulf foreign particles like bacteria and break them down using enzymes stored within small internal compartments, or ‘lysosomes’. Initial experiments using human macrophages, grown both with and without bedaquiline, showed that the drug did not harm the cells and that they grew normally. A combination of microscope imaging and genetic analysis revealed that exposure to bedaquiline not only increased the number of lysosomes within macrophage cells, but also the activity of genes and proteins that increase lysosomes’ ability to break down foreign particles. These results suggested that bedaquiline treatment might make macrophages better at fighting infection, even if the drug itself had no direct effect on bacterial cells. Further studies, where macrophages were first treated with bedaquiline and then exposed to different types of bacteria known to be resistant to the drug, confirmed this hypothesis: in every case, the treated macrophages became efficient bacterial killers. In contrast, older anti-tuberculosis drugs did not have any such potentiating effect on the macrophages. This work sheds new light on our how antibiotic drugs can interact with the cells of the human immune system, and can sometimes even boost our innate defences. Such immune-boosting effects could one day be exploited to make more effective treatments against bacterial infections.

Published
2020
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3. Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection

Author

Laura De Matteis, Anne Biton, Jesús M. de la Fuente, Brigitte Gicquel, Inés Serrano-Sevilla, Alexandre Giraud-Gatineau, Anne Danckaert, Ludovic Tailleux, Marie-Agnès Dillies, Juan Manuel Coya, Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Instituto de Nanociencia de Aragón [Saragoza, España] (INA), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad. The text represents the authors’ views and does not necessarily represent the position of the Commission who are not liable for the publication of this information. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript., European Project: 604237,EC:FP7:NMP,FP7-NMP-2013-LARGE-7,NAREB(2014), European Commission, Institut Pasteur, Diputación General de Aragón, Ministerio de Economía y Competitividad (España), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pharmaceutical Science, Medicine (miscellaneous), Mannose, 02 engineering and technology, Drug resistance, 01 natural sciences, Applied Microbiology and Biotechnology, chemistry.chemical_compound, Drug Delivery Systems, Macrophage, Cells, Cultured, Drug Carriers, Chemistry, Bacterial Infections, 021001 nanoscience & nanotechnology, 3. Good health, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:R855-855.5, Drug delivery, Host-Pathogen Interactions, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Metabolic Networks and Pathways, lcsh:Medical technology, lcsh:Biotechnology, Biomedical Engineering, Bioengineering, 010402 general chemistry, Immune system, Phagocytosis, lcsh:TP248.13-248.65, Host response, Humans, Surface grafting, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Chitosan, Innate immune system, Research, Macrophages, Mycobacterium tuberculosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, 0104 chemical sciences, MRNA Sequencing, Chitosan nanocarriers, Nanoparticles, Nanocarriers, Transcriptome
Abstract

[Background]: Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown., [Results]: Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism., [Conclusions]: The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs., This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad.

Published
2019
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4. Elaboration of a non intrusive diagnosis tool for the detection of water management defaults and CO poisoning in PEMFC stacks

Author

Steiner, N., Sébastien Wasterlain, Daniel Hissel, Denis Candusso, Harel, F., Vincent Raimbault, Pierre-Alexandre Bliman, Michel Sorine, Alexandre Giraud, Auzanneau, F., Rosini, S., Xavier François, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire des Technologies Nouvelles (INRETS/LTN), Institut National de Recherche sur les Transports et leur Sécurité (INRETS), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), SIgnals and SYstems in PHysiology & Engineering (SISYPHE), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'Electrochimie et de Physico-chimie des Matériaux et des Interfaces (LEPMI ), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire commun de recherche (FC LAB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SPI.NRJ]Engineering Sciences [physics]/Electric power, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

5. Nonlinear dynamics of fermions during preheating

Author

Alexandre Giraud, Julien Serreau, AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Inflation (cosmology), Physics, Nuclear and High Energy Physics, Field (physics), Scalar (mathematics), Yukawa potential, Astrophysics::Cosmology and Extragalactic Astrophysics, Fermion, Inflaton, symbols.namesake, Dirac fermion, Quantum electrodynamics, symbols, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Boson
Abstract

International audience; We study the role of dynamical fermions during preheating after inflation. We compute the nonequilibrium dynamics of Dirac fermions coupled to a scalar (inflaton) field at next-to-next-to-leading order in a coupling expansion of the 2PI effective action. Besides the well-known parametric production of bosons and fermions and their back-reaction on the background inflaton field, this includes direct interactions between produced particles, which have been neglected in previous studies. We present preliminary numerical results in 3+1 dimensions which indicates that, for intermediate Yukawa couplings, the latter can dramatically affect the usual picture of preheating.

Published
2009
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