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Start Over Author "Johanna Marines" Topic [sdv.bc]life sciences [q-bio]/cellular biology
2 results on '"Johanna Marines"'

1. <scp>DNA</scp> damage repair kinase <scp>DNA‐PK</scp> and <scp>cGAS</scp> synergize to induce cancer‐related inflammation in glioblastoma

Author

Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana‐Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille‐Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean‐Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), AZELEAD, Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Texas M.D. Anderson Cancer Center [Houston], Weill Cornell Medicine [Cornell University], Cornell University [New York], 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), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Institut de Recherche en Infectiologie de Montpellier (IRIM), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 637763,H2020,ERC-2014-STG,CrIC(2015), and European Project: 893772,DIM-CrIC

Subjects
DNA-PK, General Immunology and Microbiology, inflammation, [SDV]Life Sciences [q-bio], General Neuroscience, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Molecular Biology, tumor immunogenicity, General Biochemistry, Genetics and Molecular Biology, cGAS
Abstract

International audience; Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment in a glioblastoma model, a process that impairs early tumorigenesis but correlates with poor outcome in glioblastoma patients. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.

Published
2022

2. 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

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