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1. GCN2 contributes to mTORC1 inhibition by leucine deprivation through an ATF4 independent mechanism

Author

Florent Mesclon, Christopher G. Proud, Céline Jousse, Laurent Parry, Anne Catherine Maurin, Valérie Carraro, Julien Averous, Alain Bruhat, Pierre Fafournoux, Sarah Lambert-Langlais, Philippe Pierre, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Institute for Research in Biomedicine, University of Aveiro, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), University of Adelaide, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Institute for Research in Biomedicine ( iBiMED), Universidade de Aveiro, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia, Institut National de la Recherche Agronomique (INRA) Fondation ARC pour la Recherche sur le CancerIlidio Pinho foundation, Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of South Australia [Adelaide], Institut National de la Recherche Agronomique (INRA), Fondation ARC pour la Recherche sur le Cancer, Ilidio Pinho foundation, Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), ProdInra, Archive Ouverte, Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), U1104, UMR 7280, Centre d'Immunologie de Marseille-Luminy ( CIML ), Aix Marseille Université ( AMU ), Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique ( CNRS ), South Australian Health and Medical Research Institute ( SAHMRI ), and VAFFIDES, Chantal

Subjects
0301 basic medicine, Arginine, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Eukaryotic Initiation Factor-2, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mechanistic Target of Rapamycin Complex 1, Protein Serine-Threonine Kinases, Biology, Activating Transcription Factor 4, Article, Mice, 03 medical and health sciences, Leucine, preinitiation complex, translational control, pathway, mammalian target, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Food and Nutrition, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Phosphorylation, chemistry.chemical_classification, ATF3, Multidisciplinary, synthèse de protéine, ATF4, Translation (biology), muscle squelettique, Fibroblasts, Embryo, Mammalian, Amino acid, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, acide aminé, 030104 developmental biology, voluntary muscle, Biochemistry, chemistry, Alimentation et Nutrition, biological phenomena, cell phenomena, and immunity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, amino acid, Signal Transduction, expression des gènes
Abstract

It is well known that the GCN2 and mTORC1 signaling pathways are regulated by amino acids and share common functions, in particular the control of translation. The regulation of GCN2 activity by amino acid availability relies on the capacity of GCN2 to sense the increased levels of uncharged tRNAs upon amino acid scarcity. In contrast, despite recent progress in the understanding of the regulation of mTORC1 by amino acids, key aspects of this process remain unsolved. In particular, while leucine is well known to be a potent regulator of mTORC1, the mechanisms by which this amino acid is sensed and control mTORC1 activity are not well defined. Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity, indicating that leucine and arginine exert regulation via additional mechanisms. While the mechanism by which GCN2 contributes to the initial step of mTORC1 inhibition involves the phosphorylation of eIF2α, we show that it is independent of the downstream transcription factor ATF4. These data point to a novel role for GCN2 and phosphorylation of eIF2α in the control of mTORC1 by certain amino acids.

Published
2018
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2. COX-2 Inhibition Reduces Brucella Bacterial Burden in Draining Lymph Nodes

Author

Jean-Pierre Gorvel, Aurélie Gagnaire, Jean-Louis Mege, Laurent Gorvel, Kristine von Bargen, Alexia Papadopoulos, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:QR1-502, Prostaglandin, Brucella, Microbiology, lcsh:Microbiology, prostaglandins, 03 medical and health sciences, chemistry.chemical_compound, Immune system, medicine, intradermal infection, biology, Intracellular parasite, Dendritic Cells, COX-2, biology.organism_classification, 3. Good health, Interleukin 10, 030104 developmental biology, medicine.anatomical_structure, chemistry, Cervical lymph nodes, denditric cells, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Arachidonic acid, Lymph
Abstract

International audience; Brucella is a Gram-negative facultative intracellular bacterium responsible for a chronic disease known as brucellosis, the most widespread re-emerging zoonosis worldwide. Establishment of a Th1-mediated immune response characterized by the production of IL-12 and IFN gamma is essential to control the disease. Leukotrienes derived from arachidonic acid (AA) metabolism are known to negatively regulate a protective Th1 immune response against bacterial infections. Here, using genomics approaches we demonstrate that Brucella abortus strongly stimulates the prostaglandin (PG) pathway in dendritic cells (DC). We also show an induction of AA production by infected cells. This correlates with the expression of Ptgs2, a gene encoding the downstream cyclooxygenase-2 (COX-2) enzyme in infected DC. By comparing different infection routes (oral, intradermal, intranasal and conjunctival), we identified the intradermal inoculation route as the more potent in inducing Ptgs2 expression but also in inducing a local inflammatory response in the draining cervical lymph nodes (CLN). NS-398, a specific inhibitor of COX-2 enzymatic activity decreased B. melitensis burden in the CLN after intradermal infection. This effect was accompanied by a decrease of II10 and a concomitant increase of Ifng expression. Altogether, these results suggest that Brucella has evolved to take advantage of the PG pathway in the harsh environment of the CLN in order to persist and subvert immune responses. This work also proposes that novel strategies to control brucellosis may include the use of COX-2 inhibitors.

Published
2016
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3. PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma

Author

Daniel Olive, Damien Sène, Stéphanie Dogniaux, Céleste Lebbé, Asma Beldi-Ferchiou, Frank Levasseur, Claire Hivroz, Sophie Caillat-Zucman, Frédéric Vély, Marion Lambert, Eric Vivier, David Zucman, Stéphanie Dupuy, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Hôpital Foch [Suresnes], Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), ANR-13-BSV2-0018,NeuroImmunoSynapse,Trafic vésiculaire, formation et maintien des synapses neuronales et immunologiques(2013), European Project: 268537,EC:FP7:ERC,ERC-2010-AdG_20100317,THINK(2011), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, Blanc 2013 - Trafic vésiculaire, formation et maintien des synapses neuronales et immunologiques - - NeuroImmunoSynapse2013 - ANR-13-BSV2-0018 - Blanc 2013 - VALID, and The Immune function of NK cells - THINK - - EC:FP7:ERC2011-07-01 - 2016-12-31 - 268537 - VALID

Subjects
0301 basic medicine, Functional impairment, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Programmed Cell Death 1 Receptor, Tumor escape, Gene Expression, HIV Infections, NK cells, Lymphocyte Activation, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Healthy control, PD-1, Humans, Medicine, In patient, Sarcoma, Kaposi, Activating receptors, Coinfection, business.industry, Kaposi sarcoma, Herpesviridae Infections, Flow Cytometry, medicine.disease, Hepatitis C, Immunohistochemistry, Immune surveillance, Immune checkpoint, 3. Good health, Killer Cells, Natural, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, Immunology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Sarcoma, business, Biomarkers, Research Paper
Abstract

// Asma Beldi-Ferchiou 1, 2, 11 , Marion Lambert 1, 2 , Stephanie Dogniaux 3 , Frederic Vely 4, 5 , Eric Vivier 4, 5 , Daniel Olive 6 , Stephanie Dupuy 1 , Frank Levasseur 1 , David Zucman 7 , Celeste Lebbe 8 , Damien Sene 1, 2, 9 , Claire Hivroz 4 , Sophie Caillat-Zucman 1, 2, 10 1 Institut National de Recherche Medicale (INSERM) UMR1149, Centre de Recherche Sur l’Inflammation, Equipe Immunite Innee Chez l’enfant, Hopital Robert Debre, Paris, France 2 Universite Paris Diderot, Sorbonne Paris Cite, Paris, France 3 Institut Curie, Centre de Recherche, PSL Research University, INSERM U932 Immunite et Cancer, Paris, France 4 Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Universite UM2, INSERM U1104, CNRS UMR7280, Marseille, France 5 Immunologie, Hopital de la Conception, Assistance Publique- Hopitaux de Marseille, Marseille, France 6 Centre de Cancerologie de Marseille, INSERM U1068, Equipe Immunite et Cancer, Institut Paoli-Calmettes, Aix-Marseille Universite, CNRS, UMR7258, Marseille, France 7 Hopital Foch, Service de Medecine Interne, Suresnes, France 8 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Departement de Dermatologie, INSERM U976, Universite Paris Diderot, Paris, France 9 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Lariboisiere, Departement de Medecine Interne, Paris, France 10 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Laboratoire d’Immunologie, Paris, France 11 Present address: Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Henri Mondor, Laboratoire d’Immunologie, Creteil, France Correspondence to: Sophie Caillat-Zucman, email: sophie.caillat@inserm.fr Keywords: NK cells, Kaposi sarcoma, PD-1, immune checkpoint, tumor escape Received: March 31, 2016 Accepted: September 13, 2016 Published: September 20, 2016 ABSTRACT Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56 dim CD16 pos NK cells with otherwise normal expression of NK surface receptors. PD-1 pos NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1 pos NK cells failed to degranulate and release IFNγ, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro , PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i.e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance.

Published
2016
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4. Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice

Author

Garbani, M., Xia, W., Engkvist, H., Scheynius, A., Malissen, Bernard, Maurer, M., Crameri, R., Terhorst, D., Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

Annual Meeting of the European-Society-for-Dermatological-Research (ESDR), Munich, GERMANY, SEP 07-10, 2016; International audience; no abstract

Published
2016

5. Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus

Author

Gabriel V. Martin, Kiet Tiev, Brigitte Granel, Laurent Chiche, Elisabeth Diot, Eleonore C. Caillet, Marielle Martin, Nathalie C. Lambert, Isabelle Auger, Doua F. Azzouz, Fanny Arnoux, Jean Robert Harlé, Sami B. Kanaan, Thierry Martin, Jean Cabane, Nathalie Bardin, Sylvain Dubucquoi, Jean Roudier, Nathalie Balandraud, Eric Hachulla, Dominique Farge-Bancel, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Immunologie Clinique, CHU Strasbourg, Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Centre national de référence des maladies auto-immunes systémiques rares (sclérodermie systémique) [Lille], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Compétence PACA Ouest pour la prise en charge des maladies auto-immunes systémiques, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), VAFFIDES, Chantal, Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
0301 basic medicine, Male, Serum Proteins, Physiology, [SDV]Life Sciences [q-bio], Aucun, lcsh:Medicine, Biochemistry, Epitope, Scleroderma, 0302 clinical medicine, Immune Physiology, Medicine and Health Sciences, Lupus Erythematosus, Systemic, Enzyme-Linked Immunoassays, lcsh:Science, skin and connective tissue diseases, Connective Tissue Diseases, Multidisciplinary, Systemic lupus erythematosus, Immune System Proteins, Middle Aged, Blood proteins, 3. Good health, [SDV] Life Sciences [q-bio], Titer, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Ephrin Type-B Receptor 2, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, Receptor, EphB2, Immunology, Rheumatoid Arthritis, Enzyme-Linked Immunosorbent Assay, Biology, Research and Analysis Methods, Systemic Lupus Erythematosus, Sensitivity and Specificity, Antibodies, Autoimmune Diseases, 03 medical and health sciences, Exonuclease 1, Rheumatology, Diagnostic Medicine, medicine, Humans, Immunoassays, Autoantibodies, 030203 arthritis & rheumatology, Scleroderma, Systemic, Lupus Erythematosus, Arthritis, lcsh:R, Autoantibody, Biology and Life Sciences, Proteins, medicine.disease, Molecular biology, 030104 developmental biology, Epitope mapping, Exoribonucleases, Immunologic Techniques, lcsh:Q, Clinical Immunology, Clinical Medicine, Epitope Mapping
Abstract

International audience; In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10(-4)) and 60% versus 28% (P = 3.10(-8)). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10(-10)) and 82% (P = 5.10(-13)). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P< 0.0001) and correlated with disease activity (p< 0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3'-5' exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis.

Published
2016
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6. XCR1+dendritic cells promote memory CD8+T cell recall upon secondary infections

Author

Alexandre, Y., Ghilas, S., Le Bon, A., Crozat, K., Dalod, M., Sanchez, Cindy, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

7. XCR1 expression by dendritic cells promotes NK cell activation during viral infection

Author

Ghilas, S., Dalod, M., Crozat, K., Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

8. Complementarity and redundancy of innate lymphoid cells

Author

Eric Vivier, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

9. tRNAs: new regularors of immunity?

Author

Arguello, R. J., Reverendo, M., Terawaki, S., Combes, A., Vu-Manh, T. P., Santos, M., Gatti, E., Pierre, P., Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

10. Quantitative analysis of Vav1 signalosome in primary CD4 T cells identify several new Vav1 partners including CD226

Author

Gaud, G., Roncagalli, R., De Pedro, Gonzalez A., Malissen, Bernard, Saoudi, A., Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

11. A natural variant of the TCR signaling molecule Vav1 reduces both effector T cell functions and susceptibility to neuroinflammation

Author

Kassem, S., Gaud, G., Colacios, C., Bernard, I, Malisssen, B., Saoudi, A., Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

12. BAD-LAMP a novel actor of TLR9 trafficking in human plasmacytoid dendritic cells

Author

Bendriss-Vermare, N., Pierre, P., Gatti, E., Combes, A., Sari, N. Guessan P., Arguello, R., Camosseto, V., Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), VAFFIDES, Chantal, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

13. 50th Anniversary of the French Society for Immunology (SFI)

Author

Hosmalin, Anne, Sautes-Fridman, Catherine, Fougereau, Michel, Yssel, Hans, Fischer, Alain, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2016

14. NON-ACTIVATABLE MUTANT OF INHIBITOR OF KAPPA B KINASE alpha (IKK alpha) EXERTS SITE-SPECIFIC EFFECTS ON ATHEROSCLEROSIS

Author

Tilstam, Pathricia V., Theelen, Wendy, Alampour-Sarabi, Setareh, Pawig, Lukas, Asare, Yaw, Doering, Yvonne, Winther, Menno P. J., Lawrence, Toby, Zernecke, Alma, Bernhagen, Jurgen, Schober, Andreas, Jankowski, Joachim, Weber, Christian, Noels, Heidi, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

53rd ERA-EDTA Congress, Vienna, AUSTRIA, MAY 21-24, 2016; International audience; no abstract

Published
2016

15. Gene expression profiles predict treatment outcomes in Brucellosis

Author

Dufort, Matthew J., Hanniffy, Sean, Raquel Conde-Álvarez, Gorvel, Vilma Arce, Altman, Matthew C., Khaenam, Prasong, Solera, Javier, Gersuk, Vivian H., Bosilkovski, Mile, Moriyon, Ignacio, Linsley, Peter S., Gorvel, Jean-Pierre, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

Brucellosis is a zoonotic disease caused by Brucella bacteria, acquired by humans through contact with or consumption of products from infected animals. Treatment outcomes vary widely; some patients recover, others relapse, and others develop chronic symptoms despite therapy. We employed expression profiling using RNA sequencing (RNAseq) to better understand variation in outcomes and investigate disease mechanisms. We performed RNAseq analysis of whole blood samples from 125 Brucellosis patients and 51 healthy controls from Macedonia. Patients were subdivided based on disease history into primary, secondary, and chronic infection. Secondary and chronic cases did not show differences in gene expression from healthy controls or from each other. Primary cases displayed numerous transcriptional changes relative to healthy controls. Up-regulated genes were enriched for response to interferon-gamma, cytolysis, T cell proliferation, and cell cycle; down-regulated genes, for B cell proliferation. Primary cases were further subdivided based on outcome into those who resolved with treatment and those who developed disease relapse during treatment. In comparison to healthy controls, relapse cases showed larger magnitude differences in expression at diagnosis than resolution cases; this suggests that relapse could potentially be predicted based on transcription levels at time of diagnosis. Differences in gene expression observed at diagnosis were no longer present 6–9 months after diagnosis. Our results indicate opportunities to prognostically identify patients that may require more intensive treatment and monitoring, and to better understand the symptomology of and immune response to Brucella infection.

Published
2016

16. An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers

Author

Jérôme Durivault, Angélique Bole, Benoit Dérijard, Eszter Doma, Anne-Odile Hueber, Sébastien Huault, Krittalak Chakrabandhu, Ly Ta Ngoc, Kévin Lang, Michel Pierres, Jean-Pierre Gérard, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Radiothérapie [CAL, Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), This work was supported by institutional funds from the Centre National de la Recherche Scientifique (CNRS) and the Institut National de la Santé et de la Recherche Médicale (INSERM), and by grants from the Institut National du Cancer (INCa, PLBIO09-317), the University of Nice, the Agence Nationale de la Recherche (ANR-10-BLAN-1226, ANR-11-LABX-0028-01). KL was supported by funding from the Canceropole PACA, and LTN was supported by a scholarship from the ministry and education of training of the socialist republic of Vietnam., ANR-10-BLAN-1226,PLAF,Etude du rôle de la plasticité de la signalisation du récepteur Fas dans les adénocarcinomes colo-rectaux.(2010), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), VAFFIDES, Chantal, BLANC - Etude du rôle de la plasticité de la signalisation du récepteur Fas dans les adénocarcinomes colo-rectaux. - - PLAF2010 - ANR-10-BLAN-1226 - BLANC - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, UNICANCER-Université Côte d'Azur (UCA), and HUEBER, Anne-Odile

Subjects
0301 basic medicine, Cell viability testing, [SDV]Life Sciences [q-bio], Apoptosis, Protein tyrosine phosphatase, Biochemistry, Fas ligand, chemistry.chemical_compound, Aromatic Amino Acids, 0302 clinical medicine, Cell Signaling, Neoplasms, Small interfering RNAs, Post-Translational Modification, Amino Acids, Tyrosine, Biology (General), Phosphorylation, Animal Signaling and Communication, Cell Analysis, ComputingMilieux_MISCELLANEOUS, Cell Death, Animal Behavior, Organic Compounds, Kinase, Protein Tyrosine Phosphatase, Non-Receptor Type 6, General Neuroscience, Fas receptor, Endocytosis, Signaling Cascades, 3. Good health, Cell biology, Nucleic acids, [SDV] Life Sciences [q-bio], Chemistry, src-Family Kinases, Bioassays and Physiological Analysis, Cell Processes, 030220 oncology & carcinogenesis, Physical Sciences, Cell lines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biological cultures, General Agricultural and Biological Sciences, Research Article, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Molecular Sequence Data, Immunoblotting, macromolecular substances, Biology, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, 03 medical and health sciences, Apoptotic signaling cascade, Hydroxyl Amino Acids, Genetics, Humans, Amino Acid Sequence, fas Receptor, Non-coding RNA, Archived Twee, Behavior, General Immunology and Microbiology, Organic Chemistry, Chemical Compounds, Biology and Life Sciences, Proteins, Tyrosine phosphorylation, Cell Biology, Protein Structure, Tertiary, Gene regulation, Research and analysis methods, 030104 developmental biology, SW480 cells, chemistry, Mutagenesis, Site-Directed, RNA, Gene expression, Zoology
Abstract

Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive “Fas apoptosis” to “Fas multisignals” paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs) and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases., Signalling by the tumor necrosis factor receptor (TNFR) superfamily member Fas can promote either survival or death of a cell, but the mechanism underlying this choice is unclear. This study reveals that the outcome of Fas signalling (death versus survival) is determined by the tyrosine phosphorylation status of its death domain., Author Summary The versatility of the tumor necrosis factor receptor superfamily members in cell fate regulation is well illustrated by the dual signaling generated by one of the most extensively studied members of the family, Fas (CD95/TNFSFR6). Upon binding its ligand, Fas is able to elicit both pro-death and pro-survival signals. Until now, we have lacked mechanistic knowledge about when and how one signaling output of Fas is favored over the other. We demonstrate here that the outcome of Fas signaling is determined by the phosphorylation status of two tyrosine residues (Y232 and Y291) within the death domain. Dephosphorylation of Fas tyrosines by SHP-1 tyrosine phosphatase turns on the pro-apoptotic signal whereas the tyrosine phosphorylation by Src family kinases (SFKs) turns off the pro-apoptotic signal and turns on the pro-survival signal. Furthermore, we provide evidence that Fas tyrosine phosphorylation status may vary among different cancer types and influence the response to anti-cancer treatments. This information reveals an opportunity to use the screening of Fas tyrosine phosphorylation, a newly discovered direct molecular indicator of Fas functional output, to aid the design of Fas-related cancer therapies.

Published
2016
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17. Macrophage origin and self-renewal

Author

Sieweke, Michael, VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2016

18. Toward an integrative biology of T cells and dendritic cells

Author

Malissen, M., Roncagalli, R., Sandrine HENRI, Dalod, M., Luche, H., VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

Published
2016

19. Manufacturing Natural Killer Cells as Medicinal Products

Author

Christian CHABANNON, Bechara MFARREJ, Sophie GUIA DA SILVA, Sophie UGOLINI, Raynier DEVILLIER, Didier BLAISE, Eric Vivier, Boris CALMELS, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mini Review, medicine.medical_treatment, Immunology, Cellular therapy, Context (language use), Innate lymphoid cells, Human leukocyte antigen, Biology, Cell therapy, Natural Killer cells, Innate Lymphoid Cells, Immunotherapy, Immuno-oncology, Cell transplant, Manufacturing, 03 medical and health sciences, medicine, Immunology and Allergy, Cytotoxic T cell, Lymphokine-activated killer cell, Innate lymphoid cell, Natural killer T cell, 3. Good health, Cell biology, 030104 developmental biology, Natural killer cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607
Abstract

International audience; Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulated in vivo through direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing and discuss conditions in which these innovative cellular therapies can be brought to the clinic.

Published
2016
Full Text
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20. Novel microparticles create a slow releasing depot for long-term immunostimulation in allergen-specific immunotherapy

Author

Garbani, M., Xia, W., Rhyner, C., Prati, M., Scheynius, A., Bernard Malissen, Engqvist, H., Maurer, M., Crameri, R., Terhorst, D., VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

43rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung-e-V (ADF), Vienna, AUSTRIA, MAR 10-12, 2016; International audience; no abstract

Published
2016

21. Transcriptional Profiling of Type II Toxin-Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967-HP0968 System

Author

María G. Cárdenas-Mondragón, Jorge A. Girón, Sabino Pacheco, Miguel A. Ares, Margarita Camorlinga-Ponce, Javier Torres, Miguel Cruz, Leonardo G. Panunzi, VAFFIDES, Chantal, Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias [Mexico City, Mexico], Hospital de Pediatria [Mexico City, Mexico] (Centro Médico Nacional Siglo XXI)-Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departamento de Microbiología Molecular [Cuernavaca, Mexico], Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto de Biotecnología [Cuernavaca, Mexico], Centro de Detección Biomolecular [Puebla, Mexico], Benemérita Universidad Autónoma de Puebla (BUAP), This study was supported by grant FIS/IMSS/PROT/G14/1329 (to MC-M) from the Fondo de Investigación en Salud (FIS)-IMSS, México., Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS)-Hospital de Pediatria [Mexico City, Mexico] (Centro Médico Nacional Siglo XXI), National Autonomous University of Mexico - UNAM-Instituto de Biotecnología [Cuernavaca, Mexico], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Microbiology (medical), [SDV.IMM] Life Sciences [q-bio]/Immunology, Operon, lcsh:QR1-502, Virulence, medicine.disease_cause, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Transcription (biology), medicine, Environmental cues, Gene, biology, H pylori, Pathogenic bacteria, toxin–antitoxin system, HP0967, Toxin-antitoxin system, Helicobacter pylori, biology.organism_classification, HP0968, 3. Good health, 030104 developmental biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antitoxin, H. pylori
Abstract

International audience; Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylon in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of pylon 26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895. Here we characterized a heretofore undescribed type II TA system in H. pylori, HP0967-HP0968, which is encoded by the bicistronic operon hp0968-hp0967 and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed in H. pylori during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the hp0968-hp0967 pair was the most affected under these environmental conditions. Transcription of hp0968-hp0967 was strongly induced in a mature H. pylori biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The hp0968-hp0967 TA system was the most frequent among 317 H. pylori strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in H. pylori under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a bona fide type II TA system in H. pylori, whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.

Published
2016
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22. Natural Killer Cells Preface

Author

Eric Vivier, Di Santo, James, Moretta, Alessandro, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vivier, E and DiSanto, J and Moretta, VAFFIDES, Chantal, Vivier, E and DiSanto, J and Moretta, A, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2016

23. gamma delta T cells support gut Ag-reactive colitogenic effector T-cell generation by enhancing Ag presentation by CD11b(+) DCs in the mesenteric LN

Author

Do, Jeong-Su, Visperas, Anabelle, Freeman, Michael L., Jang, Eunjung, Kim, Sohee, Bernard Malissen, Min, Booki, VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

Annual Meeting of the American-Association-of-Immunologists (AAI), Seattle, WA, MAY 13-17, 2016; International audience; no abstract

Published
2016

24. Interactomics and structure-function analysis of the RLTPR protein underpin its essential role for costimulation via CD28 in mouse and human T cells

Author

Malissen, M., Roncagalli, R., Cucchetti, M., Bergot, E., Jarmuzynski, N., Gregoire, C., Menoita, Goncalves M., Liang, Y., Malissen, Bernard, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and VAFFIDES, Chantal

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG 21-26, 2016; International audience; no abstract

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