Search

Your search keyword '"Johanna Marines"' showing total 3 results
Start Over Author "Johanna Marines" Topic 0302 clinical medicine
3 results on '"Johanna Marines"'

1. Nucleic Acid Immunity and DNA Damage Response: New Friends and Old Foes

Author

Clara Taffoni, Alizée Steer, Johanna Marines, Hanane Chamma, Isabelle K. Vila, Nadine Laguette, Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, cGAS-STING, DNA damage, Mini Review, [SDV]Life Sciences [q-bio], Immunology, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, DNA-PK, 03 medical and health sciences, Cytosol, 0302 clinical medicine, Immune system, Interferon, Nucleic Acids, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Immunology and Allergy, cytosolic nucleic acids, IFI16, Innate immune system, Pattern recognition receptor, Membrane Proteins, RC581-607, Immunity, Innate, 3. Good health, Cell biology, body regions, tumorigenesis, Crosstalk (biology), 030104 developmental biology, inflammation, Receptors, Pattern Recognition, 030220 oncology & carcinogenesis, Nucleic acid, Immunologic diseases. Allergy, DNA damage responses, DNA Damage, Signal Transduction, medicine.drug
Abstract

International audience; The maintenance of genomic stability in multicellular organisms relies on the DNA damage response (DDR). The DDR encompasses several interconnected pathways that cooperate to ensure the repair of genomic lesions. Besides their repair functions, several DDR proteins have emerged as involved in the onset of inflammatory responses. In particular, several actors of the DDR have been reported to elicit innate immune activation upon detection of cytosolic pathological nucleic acids. Conversely, pattern recognition receptors (PRRs), initially described as dedicated to the detection of cytosolic immune-stimulatory nucleic acids, have been found to regulate DDR. Thus, although initially described as operating in specific subcellular localizations, actors of the DDR and nucleic acid immune sensors may be involved in interconnected pathways, likely influencing the efficiency of one another. Within this mini review, we discuss evidences for the crosstalk between PRRs and actors of the DDR. For this purpose, we mainly focus on cyclic GMP-AMP (cGAMP) synthetase (cGAS) and Interferon Gamma Inducible Protein 16 (IFI16), as major PRRs involved in the detection of aberrant nucleic acid species, and components of the DNA-dependent protein kinase (DNA-PK) complex, involved in the repair of double strand breaks that were recently described to qualify as potential PRRs. Finally, we discuss how the crosstalk between DDR and nucleic acid-associated Interferon responses cooperate for the fine-tuning of innate immune activation, and therefore dictate pathological outcomes. Understanding the molecular determinants of such cooperation will be paramount to the design of future therapeutic approaches.

Published
2021

2. Sting orchestrates the crosstalk between polyunsaturated fatty acids metabolism and inflammatory responses

Author

Xavier Bonnefont, Andrei Turtoi, Hanane Chamma, Alizée Steer, Isabelle K. Vila, Johanna Marines, Dimitrios Vlachakis, Nadine Laguette, Mathilde Saccas, Clara Taffoni, Lei Jin, Line S. Reinert, Søren R. Paludan, and Evgenia Turtoi

Subjects
chemistry.chemical_classification, 0303 health sciences, FADS2, Inflammation, Biology, eye diseases, Cell biology, 03 medical and health sciences, Sting, 0302 clinical medicine, Immune system, Fatty acid desaturase, chemistry, 030220 oncology & carcinogenesis, Stimulator of interferon genes, medicine, biology.protein, medicine.symptom, Homeostasis, 030304 developmental biology, Polyunsaturated fatty acid
Abstract

SummaryInflammatory disorders are major health issues in which immune function and metabolic homeostasis are concertedly altered. Yet, the molecular mechanisms coordinating innate and metabolic pathways in homeostatic conditions are poorly understood. Here, we unveil a negative regulatory feedback loop involving the Stimulator of interferon genes (Sting) and the Fatty acid desaturase 2 (Fads2). At steady state, Sting regulates FA metabolism by repressing the activity of the Fads2 enzyme responsible for the desaturation of polyunsaturated FAs (PUFAs). Importantly, Sting activation increased Fads2 activity, while antagonizing Fads2 enhanced Sting activation, promoting the establishment of an anti-viral state. Remarkably, the cross-regulation between Sting and Fads2 is mediated by the cyclic GMP-AMP (cGAMP) Sting agonist and PUFAs. Indeed, we found that PUFAs inhibit Sting activation, while Sting agonists bind Fads2. Thus, our study identifies Sting as a master regulator of FA metabolism, and PUFAs as modulators of Sting-dependent inflammation. The interplay between Fads2 and Sting determines the fine-tuning of inflammatory responses, but comes at the expense of metabolic alterations, which are critical to consider in human pathologies associated with aberrant Sting activation.

Published
2020

3. STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses

Author

Isabelle K. Vila, Hanane Chamma, Alizée Steer, Mathilde Saccas, Clara Taffoni, Evgenia Turtoi, Line S. Reinert, Saqib Hussain, Johanna Marines, Lei Jin, Xavier Bonnefont, Mathieu Hubert, Olivier Schwartz, Soren R. Paludan, Gaetan Van Simaeys, Gilles Doumont, Bijan Sobhian, Dimitrios Vlachakis, Andrei Turtoi, Nadine Laguette, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Aarhus University [Aarhus], Albany Medical College, Institut de Génomique Fonctionnelle (IGF), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Aarhus University Hospital, Center for Microscopy and Molecular Imaging (IBMM - CMMI), Université libre de Bruxelles (ULB), Agricultural University of Athens, Biomedical Research Foundation of the Academy of Athens (BRFAA), National and Kapodistrian University of Athens (NKUA), We acknowledge the SIRIC Montpellier Cancer grant (INCa_Inserm_DGOS_12553), Metamus-RAM and iExplore-RAM animal facilities, the Laboratoire de Mesures Physiques of the University of Montpellier for access to the MS instruments, the MRI imaging facility, member of the national infrastructure France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04, 'Investments for the future'), and Ross Tomaino from the Taplin Mass Spectrometry Facility of Harvard Medical School for MS analysis. We thank T. Emilien, A. Sedda, C. de Maeseneire, N. Passon, and C. Van Heymbeek for their contribution. We thank the Cyclotron team from the Erasme Hospital, Brussels, Belgium, for the FDG provision. Work in N.L.’s laboratory is supported by the European Research Council (ERC-Stg CrIC: 637763, ERC-PoC DIM-CrIC: 893772), la Ligue pour la Recherche contre le Cancer, and the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS: ECTZ117448). H.C. is supported by a PhD fellowship from la Ligue pour la Recherche contre le Cancer. C.T. is supported by the Merck Sharp and Dohme Avenir (MSD-Avenir – GnoSTic) program and an ANRS fellowship (ECTZ119088). J.M. is supported by a Conventions Industrielles de Formation par la Recherche (CIFRE) fellowship from the Agence Nationale de Recherche Technologie (ANRT). A.S. is supported by the ERC-PoC DIM-CrIC (893772). I.K.V. is supported by the ERC-Stg CrIC (637763) and the Fondation pour la Recherche Médicale (ARF20170938586). Work in S.R.P.’s laboratory is supported by the European Research Council (ERC-AdG ENVISION, 786602), the Novo Nordisk Foundation (NNF18OC0030274), and the Lundbeck Foundation (R198-2015-171 and R268-2016-3927). Work in A.T.’s laboratory is supported by a SIRIC Montpellier Cancer grant (INCa_Inserm_DGOS_12553), the Fondation de France (grant no. 00078461), and a LabEx MabImprove Starting Grant. X.B. is supported by ANR GH-gen (ANR-18-CE14-0017). The Center for Microscopy and Molecular Imaging (CMMI) is supported by the European Regional Development Fund (ERDF), the Walloon Region, the Fondation ULB, the Fonds Erasme, and Association Vinçotte Nuclear (AVN). G.D. is supported by the European Regional Development Fund (ERDF) and the Walloon Region. Work in O.S.’s lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and IDISCOVR, Fondation pour la Recherche Médicale. Schematic representations were created with https://biorender.com, We thank M. Benkirane, G. Cavalli, J. Déjardin, and B. de Massy for discussions and comments. We thank C. Goujon and B. Bonaventure for CRISPR/Cas9 gRNA sequences., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), ANR-18-CE14-0017,GH-Gen,Origine et fonction du generateur hypophysaire de pulses d'hormone de croissance(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-20-COVI-0062,proteoCOVID,Protéomique clinique de la protéine SARS-CoV-2 Spike pour optimiser sa détection et le développement de tests sérologiques(2020), European Project: 637763,H2020,ERC-2014-STG,CrIC(2015), European Project: 893772,DIM-CrIC, European Project: 786602,ENVISION, Virus et Immunité - Virus and immunity, Guerineau, Nathalie C., Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Laboratoires d'excellence - Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used - - MAbImprove2010 - ANR-10-LABX-0053 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Origine et fonction du generateur hypophysaire de pulses d'hormone de croissance - - GH-Gen2018 - ANR-18-CE14-0017 - AAPG2018 - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Protéomique clinique de la protéine SARS-CoV-2 Spike pour optimiser sa détection et le développement de tests sérologiques - - proteoCOVID2020 - ANR-20-COVI-0062 - COVID-19 - VALID, Molecular basis of the cross-talk between chronic inflammation and cancer - CrIC - - H20202015-04-01 - 2020-03-31 - 637763 - VALID, Decreasing Pancreatic Adenocarcinoma-related Inflammation using small molecule inhibitors of STING - DIM-CrIC - 893772 - INCOMING, Novel mechanisms of early defense against virus infections - ENVISION - 786602 - INCOMING, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AZELEAD, 377 Rue du Professeur Blayac, 34080 Montpellier, France, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Fatty Acid Desaturases, Physiology, [SDV]Life Sciences [q-bio], nucleic acid immunity, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, cytosolic DNA, Article, 03 medical and health sciences, 0302 clinical medicine, delta-6 Desaturase, Humans, FADS2, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, 030304 developmental biology, Inflammation, Metabolic Syndrome, interferon responses, 0303 health sciences, Cell Biology, Lipid Metabolism, eye diseases, 3. Good health, [SDV] Life Sciences [q-bio], Fatty Acids, Unsaturated/metabolism, inflammation, 030220 oncology & carcinogenesis, Fatty Acids, Unsaturated, metabolism, Fatty Acid Desaturases/genetics, STING, cGAS, polyunsaturated fatty acids
Abstract

Summary Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the STING (stimulator of interferon genes) protein regulates metabolic homeostasis through inhibition of the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in polyunsaturated fatty acid (PUFA) desaturation. STING ablation and agonist-mediated degradation increased FADS2-associated desaturase activity and led to accumulation of PUFA derivatives that drive thermogenesis. STING agonists directly activated FADS2-dependent desaturation, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolving STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING-targeting therapies., Graphical abstract, Highlights • STING inhibits FADS2-dependent desaturation of PUFAs and LC-PUFAs • STING activation leads to upregulation of FADS2-associated desaturase activity • STING agonists activate FADS2-dependent PUFA and LC-PUFA desaturation • PUFAs inhibit STING-dependent inflammatory responses, The stimulator of interferon genes (STING) is a central regulator of nucleic acid-associated inflammatory responses. Here, Vila et al. discover that STING regulates polyunsaturated fatty acid (PUFA) metabolism, and in turn, PUFAs inhibit STING-dependent inflammation. This cross-regulation is central to the maintenance of metabolic homeostasis.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results