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1. Cathepsin C inhibition as a potential treatment strategy in cancer

Author

Anne-Sophie Lamort, Artur Giełdoń, Aö Yildirim, Moez Rhimi, Céline Beauvillain, Dieter E. Jenne, Georgios T. Stathopoulos, Roxane Domain, Brice Korkmaz, Ralph Kettritz, Bernardo, Elizabeth, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ludwig Maximilian University [Munich] (LMU), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), University of Gdańsk (UG), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]

Subjects
Cancer, Inflammation, Inhibitor, Neutrophil, Protease, Treatment Strategy, Proteases, Neutrophils, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Cathepsin G, Biology, medicine.disease_cause, Biochemistry, Extracellular Traps, Cathepsin C, Protein Structure, Secondary, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, Proteinase 3, Neoplasms, medicine, Tumor Microenvironment, Animals, Humans, Pharmacology, Proteolytic enzymes, Neutrophil extracellular traps, medicine.disease, Protein Structure, Tertiary, Treatment strategy, chemistry, Cancer research, Inflammation Mediators, Serine Proteases, Carcinogenesis
Abstract

International audience; Epidemiological studies established an association between chronic inflammation and higher risk of cancer. Inhibition of proteolytic enzymes represents a potential treatment strategy for cancer and prevention of cancer metastasis. Cathepsin C (CatC) is a highly conserved lysosomal cysteine dipeptidyl aminopeptidase required for the activation of pro-inflammatory neutrophil serine proteases (NSPs, elastase, proteinase 3, cathepsin G and NSP-4). NSPs are locally released by activated neutrophils in response to pathogens and non-infectious danger signals. Activated neutrophils also release neutrophil extracellular traps (NETs) that are decorated with several neutrophil proteins, including NSPs. NSPs are not only NETs constituents but also play a role in NET formation and release. Although immune cells harbor large amounts of CatC, additional cell sources for this protease exists. Upregulation of CatC expression was observed in different tissues during carcinogenesis and correlated with metastasis and poor patient survival. Recent mechanistic studies indicated an important interaction of tumor-associated CatC, NSPs, and NETs in cancer development and metastasis and suggested CatC as a therapeutic target in a several cancer types. Cancer cell-derived CatC promotes neutrophil recruitment in the inflammatory tumor microenvironment. Because the clinical consequences of genetic CatC deficiency in humans resulting in the elimination of NSPs are mild, small molecule inhibitors of CatC are assumed as safe drugs to reduce the NSP burden. Brensocatib, a nitrile CatC inhibitor is currently tested in a phase 3 clinical trial as a novel anti-inflammatory therapy for patients with bronchiectasis. However, recently developed CatC inhibitors possibly have protective effects beyond inflammation. In this review, we describe the pathophysiological function of CatC and discuss molecular mechanisms substantiating pharmacological CatC inhibition as a potential strategy for cancer treatment.

Published
2021

2. Performance criteria for the verification of IgE and tryptase assay methods: recommendations from the AllergoBioNet network

Author

M. Vivinus, Marie-Alexandra Alyanakian, P.A. Apoil, Arnaud Cirée, Anthony Léon, Angélique Grenier, Pascale Nicaise-Roland, Thierry Tabary, Valérie Guérin, Stéphanie Rogeau, Anne Sarrat, Béatrice Uring-Lambert, Martine Pernollet, Lorna Garnier, Pascale Chrétien, Delphine Mariotte, Remy Couderc, Erwan Dumontet, Bertrand Evrard, Benoît Cypriani, Lionel Chollet, Caroline Hémont, Joana Vitte, Céline Beauvillain, CHU Bordeaux [Bordeaux], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie biologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer, Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de biochimie médicale [CHRU Besançon, hôpital Minjoz], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Biologie intégrative des organismes marins (BIOM), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité Fonctionnelles d′Immunologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche en Nanosciences - EA 4682 (LRN), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Archet 2 [Nice] (CHU), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service d'Allergologie pédiatrique [CHU Trousseau], CHU Toulouse [Toulouse], Hôpitaux Universitaires Paris Sud, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)

Subjects
medicine.medical_specialty, Consensus, Computer science, media_common.quotation_subject, [SDV]Life Sciences [q-bio], tryptase, Fidelity, Tryptase, Immunoglobulin E, In vitro diagnostic, Accreditation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Medical physics, quality control, 030304 developmental biology, media_common, 0303 health sciences, biology, Diagnostic Tests, Routine, Total ige, Reproducibility of Results, specific IgE antibodies, General Medicine, Repeatability, allergy, 3. Good health, total IgE, Technical performance, 030228 respiratory system, biology.protein, Measurement uncertainty, Biological Assay, Tryptases, France, Laboratories
Abstract

International audience; Accreditation of an in vitro diagnostic assay according to the NHENI/ISO 15189 standard requires to analyze its technical performance before implementation for routine use, and annually when reviewing effectiveness of quality controls. Performance is evaluated through repeatability, intermediate fidelity, accuracy and uncertainty of measurement. The coefficients of variation (CV) of the infra-assay and inter-assay precision tests must be compared with those of ``peers'' (results from laboratories employing the same method) and also with those obtained with ``all methods'', i.e., results from all laboratories performing the same assay, irrespective of the method. To our best knowledge, there is currently no French or international recommendation on what the acceptable limits of performance for specific IgE and tryptase assays should be. Therefore, the AllergoBioNet network of hospital allergy laboratories set out to characterize the performance of their current methods as a basis for the development of recommendations. The results provided by 24 centers were analyzed and led to consensus recommendations for specific IgE, total and tryptase assays.

Published
2020

3. Lactic acidosis together with GM-CSF and M-CSF induces human macrophages toward an inflammatory pro-tumor phenotype

Author

Laurence Preisser, Pedro Raro, Clément Adam, Pascale Pignon, Vincent Procaccio, Vincent Lavoué, Alain Morel, Philippe Descamps, Simon Blanchard, Cinzia Bocca, Valérie Seegers, Céline Beauvillain, Romuald Wernert, Judith Kouassi Nzoughet, Léa Paolini, Norbert Ifrah, Pascale Jeannin, Véronique Verrielle, Yves Delneste, Mario Campone, Véronique Catros, Louise-Marie Chevalier, Guy Lenaers, Guillaume Tcherkez, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Canberra, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), INCa-DGOS-Inserm_12558, Ministry of Health and the Institute for Health and Medical Research, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Immunologie et d'Allergologie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Australian National University (ANU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), SIRIC ILIAD program (National Cancer Institute, Ministry of Health and the Institute for Health and Medical Research, INCa-DGOS-Inserm_12558)Ligue contre le Cancer (comitée du Maine et Loire, Angers, France) and the regional council of Pays de la Loire (Canceropole Grand-Ouest, projects PlasTICO and Concerto), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Stress Adaptation and Tumor Escape in breast cancer - SATE (CRCINA - Département ONCO - Equipe 8), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Université d'Angers (UA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Blanchard, Simon, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID

Subjects
0301 basic medicine, Cancer Research, Chemokine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Monocytes, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Tumor Cells, Cultured, medicine, Humans, cancer, Interleukin 8, Autocrine signalling, ComputingMilieux_MISCELLANEOUS, Ovarian Neoplasms, lactate, biology, Chemistry, Macrophage Colony-Stimulating Factor, Macrophages, Granulocyte-Macrophage Colony-Stimulating Factor, Cell Differentiation, GM-CSF, medicine.disease, M-CSF, 3. Good health, Interleukin 10, Phenotype, 030104 developmental biology, inflammation, 030220 oncology & carcinogenesis, Monocyte differentiation, Lactic acidosis, biology.protein, Cancer research, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Acidosis, Lactic, Female, medicine.symptom
Abstract

In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including protumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines, and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the protumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.

Published
2020

4. Antigen 5–spiked Vespula and Polistes venom extracts for Vespid allergy diagnostics: A French multicenter study

Author

Claude Lambert, M. Drouet, Françoise Bienvenu, P.A. Apoil, Charles Dzviga, Thierry Tabary, D. Mariotte, Séverine Brabant, Laurence Guilloux, François Lavaud, Anne Sarrat, Joana Vitte, Pascale Nicaise-Roland, Joëlle Birnbaum, Céline Beauvillain, Nicolas Hutt, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Eurofins Biomnis, Laboratoire d'Immunologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité Fonctionnelles d′Immunologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Male, 0301 basic medicine, Allergy, MESH: Immunoglobulin E / blood, Wasps, Wasp Venoms, Venom, Vespula, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, MESH: Aged, 80 and over Allergens / immunology, Immunology and Allergy, MESH: Animals, MESH: Hypersensitivity / immunology, Child, Aged, 80 and over, MESH: Aged, MESH: Immunoglobulin E / immunology, MESH: Middle Aged, biology, Middle Aged, MESH: Infant, MESH: Young Adult, Child, Preschool, Female, France, Polistes, MESH: Wasp Venoms / immunology, MESH: Wasps / immunology, Adult, Pulmonary and Respiratory Medicine, Adolescent, Immunology, Young Adult, 03 medical and health sciences, Antigen, Hypersensitivity, medicine, Animals, Humans, MESH: Hypersensitivity / blood, Aged, MESH: Adolescent, MESH: Hypersensitivity / diagnosis, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, MESH: Adult, Polistes spp, Allergens, Immunoglobulin E, biology.organism_classification, medicine.disease, MESH: Male, MESH: France, 030104 developmental biology, 030228 respiratory system, Multicenter study, business, MESH: Female
Abstract

International audience; Vespula and Polistes spp venom extracts (VEs) for ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden) platforms have beenspiked, that is, enriched, with group 5 allergens since 2012. Limited information was available from the manufacturer, but small cohortshave reported altered performance for in vitro diagnostics.1,2 Herein we present the results of a French multicenter study onantigen 5–spiked Vespula and Polistes VEs compared with nonspiked VEs

Published
2018

5. Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells

Author

Léa Paolini, Olivier Adotevi, Maud Charpentier, E Dupel, Agnès Fortun, Emilie Dupré, Catherine Rabu, Nathalie Labarrière, Céline Beauvillain, L. Rangan, Jean-Baptiste Latouche, François Lang, Laetitia Florenceau, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), This work was carried out with the support of the LabEx IGO project (n° ANR-11-LABX-0016–01) funded by the «Investissements d’Avenir» French Government program, managed by the French National Research Agency (ANR)., ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Bernardo, Elizabeth, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Nantes Université (Nantes Univ)

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Peptide, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Biology, Cancer vaccines, lcsh:RC254-282, Epitope, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, medicine, melanoma, Immunology and Allergy, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Original Research, chemistry.chemical_classification, Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, synthetic long peptides, 3. Good health, Vaccination, 030104 developmental biology, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, lcsh:RC581-607
Abstract

International audience; There is now a consensus that efficient peptide vaccination against cancer requires that peptides should (i) be exclusively presented by professional APC and (ii) stimulate both CD4 and CD8-specific T cell responses. To this aim, in recent trials, patients were vaccinated with pools of synthetic long peptides (SLP) (15-30 aa long) composed of a potential class I epitope(s) elongated at both ends with native antigen sequences to also provide a potential class II epitope(s). Using MELOE-1 as a model antigen, we present an alternative strategy consisting in linking selected class I and class II epitopes with an artificial cathepsin-sensitive linker to improve epitope processing and presentation by DC. We provide evidence that some linker sequences used in our artificial SLPs (aSLPs) could increase up to 100-fold the cross-presentation of class I epitopes to CD8-specific T cell clones when compared to cross-presentation of the corresponding native long peptide. Presentation of class II epitopes were only slightly increased. We confirmed this increased cross-presentation after in vitro stimulation of PBMC from healthy donors with aSLP and assessment of CD8-specific responses and also in vivo following aSLP vaccination of HLA*A0201/HLA-DRB0101 transgenic mice. Finally, we provide some evidence that vaccination with aSLP could inhibit the growth of transplanted tumors in mice. Our data thus support the use of such aSLPs in future cancer vaccination trials to improve anti-tumor CD8 T cell responses and therapeutic efficacy. ARTICLE HISTORY

Published
2019

7. Anti-pentraxin antibodies in autoimmune systemic diseases: Focus on anti-pentraxin-3 autoantibodies

Author

Céline Beauvillain, Caroline Poli, Alain Chevailler, Jean-François Augusto, Jean-François Subra, Sébastien Jaillon, Xavier Puéchal, Yves Delneste, Gilles Renier, Pascale Jeannin, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), Laboratoire d'Immunologie et d'Allergologie [CHU Angers], Department of Immunology and Inflammation [Rozzano, Milan, Italy], University of Milan-Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by institutional grants (Inserm, University of Angers and GIRCI GrandOuest) and a grant fromthe Agence Nationale de la Recherche (project Pentraximmune)., Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Università degli Studi di Milano = University of Milan (UNIMI)-Humanitas Clinical and Research Center [Rozzano, Milan, Italy]

Subjects
0301 basic medicine, Immunology, Autoimmunity, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Ligands, medicine.disease_cause, Autoantigens, Immune tolerance, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pentraxins, Immune Tolerance, Prevalence, medicine, Humans, Immunology and Allergy, autoimmune diseases, Autoantibodies, 030203 arthritis & rheumatology, biology, business.industry, Autoantibody, biomarkers, PTX3, 3. Good health, Antibody opsonization, Serum Amyloid P-Component, anti-pentraxin autoantibodies, C-Reactive Protein, 030104 developmental biology, Multigene Family, pentraxin-3, biology.protein, medicine.symptom, Antibody, business
Abstract

International audience; Pentraxins are soluble pattern recognition molecules implicated not only in the opsonization and removal of microorganisms but also in the clearance of modified self (i.e., dying cells). Pentraxins can be classified into short pentraxins (C-reactive protein and serum amyloid-P component) and long pentraxins with pentraxin-3 (PTX3), the prototypic one of the latter. Pentraxins are involved in various physiological or pathophysiological processes such as inflammation and autoimmunity. A breakdown in immune tolerance to pentraxins has been reported in various autoimmune diseases. In the present review,we analyzed the current knowledge concerning anti-pentraxin antibodies,with a special focus on anti-PTX3 autoantibodies.

Published
2017

8. FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Author

Céline Beauvillain, Laurent Marsollier, Caroline Savary, Yves Delneste, Estelle Marion, Camille Cano, Frédéric Altare, Pascale Jeannin, Ulrich Jarry, Laurence Preisser, Marie Robbe-Saule, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de pathologie cellulaire et Tissulaire, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'Immunologie et d'Allergologie, Université d'Angers - Faculté de médecine (UA UFR Médecine), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Buruli ulcer, Remission, Spontaneous, 030106 microbiology, Immunology, Mice, Inbred Strains, Spontaneous remission, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, Species Specificity, [SDV.CAN] Life Sciences [q-bio]/Cancer, Immunity, medicine, Animals, Humans, Immunology and Allergy, Mycolactone, Buruli Ulcer, Mice, Inbred BALB C, Innate immune system, Mycobacterium ulcerans, Gene Expression Regulation, Bacterial, medicine.disease, biology.organism_classification, Immunity, Innate, Pathophysiology, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Host-Pathogen Interactions, Macrolides
Abstract

Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies.

Published
2016

9. Immunosénescence : vieillissement « et » ou « du » système immunitaire

Author

Caroline Poli, Pascale Jeannin, Alain Chevailler, Céline Beauvillain, Gilles Renier, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Gynecology, 03 medical and health sciences, Medical Laboratory Technology, medicine.medical_specialty, 030104 developmental biology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biochemistry (medical), medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 3. Good health, Analytical Chemistry
Abstract

International audience; La plus grande sensibilité aux infections, aux tumeurs, aux maladies auto-immunes et la moins bonne réponse vaccinale sont les caractéristiques de la réponse immunitaire du sujet âgé. Cette tranche de population en pleine expansion jusqu'en 2014 dans les sociétés industrielles, présente une plus grande fréquence de comorbidités, qui sont autant de facteurs aggravants de la déficience de la réponse immunitaire identifiée sous le vocable d'immunosénescence. Pour en rendre compte, il faut envisager la dialectique de la participation du système immunitaire au processus de vieillissement physiologique et les conséquences de ce dernier sur la réponse immunitaire dans ses branches innée et adaptative, avec des facteurs génétiques, épigénétiques et environnementaux intriqués. L'étude de nombreux paramètres immunitaires a permis d'identifier comme facteurs prédictifs de vieillissement du système immunitaire une plus grande fréquence de lymphocytes T CD8+CD28-, une faible réponse proliférative, un rapport CD4/CD8 bas (< 1), un nombre de lymphocytes B2 diminué et une séropositivité pour le CMV. Réponse immunitaire-télomère-vieillissement.

Published
2016

10. CCR7 is involved in the migration of neutrophils to lymph nodes

Author

Pierre Cunin, Pascale Jeannin, Krzysztof Masternak, Sébastien Jaillon, Andrea Doni, Céline Beauvillain, Yves Delneste, Alain Chevailler, Giovanni Magistrelli, Mari Scotet, Marie Line Loiry, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Receptors, CCR7, Neutrophils, [SDV]Life Sciences [q-bio], Immunology, chemical and pharmacologic phenomena, C-C chemokine receptor type 7, Biology, Biochemistry, Mice, 03 medical and health sciences, Chemokine receptor, 0302 clinical medicine, Immune system, Cell Movement, medicine, Animals, Humans, Lymph node, Cells, Cultured, 030304 developmental biology, Mice, Knockout, 0303 health sciences, CCL19, hemic and immune systems, Cell migration, Cell Biology, Hematology, 3. Good health, Mice, Inbred C57BL, Chemotaxis, Leukocyte, medicine.anatomical_structure, Neutrophil Infiltration, Lymph Nodes, Lymph, 030215 immunology, CCL21
Abstract

Increasing evidence suggests that neutrophils may participate in the regulation of adaptive immune responses, and can reach draining lymph nodes and cross-prime naive T cells. The aim of this study was to identify the mechanism(s) involved in the migration of neutrophils to the draining lymph nodes. We demonstrate that a subpopulation of human and mouse neutrophils express CCR7. CCR7 is rapidly expressed at the membrane upon stimulation. In vitro, stimulated human neutrophils migrate in response to the CCR7 ligands CCL19 and CCL21. In vivo, injection of complete Freund adjuvant induces a rapid recruitment of neutrophils to the lymph nodes in wild-type mice but not in Ccr7−/− mice. Moreover, intradermally injected interleukin-17–and granulocyte-macrophage colony-stimulating factor–stimulated neutrophils from wild-type mice, but not from Ccr7−/− mice, migrate to the draining lymph nodes. These results identify CCR7 as a chemokine receptor involved in the migration of neutrophils to the lymph nodes.

Published
2011

11. Neonatal and adult microglia cross-present exogenous antigens

Author

Yves Delneste, Pascale Jeannin, Ulrich Jarry, Dominique Couez, Hugues Gascan, Céline Beauvillain, Pierre Guermonprez, Mari Scotet, and Sabrina Donnou

Subjects
Aging, Proteasome Endopeptidase Complex, Ovalbumin, CD8 Antigens, T-Lymphocytes, Antigen presentation, Antigen-Presenting Cells, Genes, MHC Class I, Mice, Transgenic, Major histocompatibility complex, Cell Line, Mice, Cellular and Molecular Neuroscience, Antigen, MHC class I, medicine, Animals, Antigens, Antigen-presenting cell, Cells, Cultured, Neuroinflammation, Inflammation, biology, Microglia, Flow Cytometry, Cell biology, Mice, Inbred C57BL, Phenotype, medicine.anatomical_structure, Animals, Newborn, Neurology, Immunology, biology.protein, CD8
Abstract

Some observations have suggested that cells from the central nervous system (CNS) could present exogenous antigens on major histocompatibility complex (MHC) class I molecules to CD8(+) T cells (a process called cross-presentation). Microglia are the major myeloid immunocompetent cells of the CNS. When activated, following the injury of the nervous parenchyma, they become fully competent antigen-presenting cells (APC) that prime CD4(+) T lymphocytes. We therefore tested the cross-presentation capacity of murine microglia. We report that a microglial cell line (C8-B4), neonatal microglia, and interestingly adult microglia cross-present soluble exogenous antigen (ovalbumin) to a OVA-specific CD8(+) T-cell hybridoma and cross-prime OVA-specific naive OT-1 CD8(+) T cells. In both these cases, C8-B4 and neonatal microglia cross-present OVA as well as peritoneal macrophages. Although cross-presentation by adult microglia is less efficient, it is increased by GM-CSF and CpG oligodeoxynucleotide (ODN) stimulation. Using microglial cells either exposed to an inhibitor of proteasome, lactacystin, or purified from TAP(-/-) mice, we demonstrate that the microglia cross-present antigen in proteasome- and TAP-dependant pathways, respectively. Last, microglia purified from adult mice injected intracerebrally with OVA efficiently stimulate OVA-specific CD8(+) T cells, thereby showing that microglia take up and process exogenous antigen into MHC class I in vivo. This first demonstration of the cross-presentation property of microglia offers novel therapeutic approaches to modulate CD8 T-cell responses in the brain.

Published
2008

12. PPARα regulates endothelial progenitor cell maturation and myeloid lineage differentiation through a NADPH oxidase-dependent mechanism in mice

Author

Abderahim Gaceb, Ramaroson Andriantsitohaina, M. Carmen Martinez, Emilie Lauret, Céline Beauvillain, Luisa Vergori, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bari Aldo Moro (UNIBA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), and Université d'Angers (UA)-Université de Nantes (UN)

Subjects
Male, Myeloid, [SDV]Life Sciences [q-bio], Population, Biology, Endothelial progenitor cell, Mice, Cell Movement, Bone Marrow, medicine, Animals, Cell Lineage, PPAR alpha, Progenitor cell, education, hematopoietic progenitors, Cells, Cultured, Endothelial Progenitor Cells, Mice, Knockout, education.field_of_study, NADPH oxidase, NADPH Oxidases, Cell Differentiation, Cell Biology, differentiation, Cell biology, Endothelial stem cell, Mice, Inbred C57BL, medicine.anatomical_structure, biology.protein, endothelial cell, Molecular Medicine, Bone marrow, Stem cell, Developmental Biology
Abstract

Peroxisome proliferator-activated receptor-alpha (PPARα) is a key modulator of lipid metabolism. Here, we propose that PPARα regulates the maturation and function of bone marrow (BM) progenitor cells. Although PPARα deletion increased the number of BM-resident cells and the differentiation of endothelial progenitor cells (EPCs) and monocytic progenitor cells, it impaired re-endothelialization of injured carotid artery that was associated with reduced circulating EPCs. Also, PPARα deletion diminished the in vivo proangiogenic effect of PPARα agonist without affecting EPC differentiation markers. Macrophage colony-stimulating factor treatment increased the population of monocytic progenitor cells as well as secretome of BM-derived cells in PPARα wild-type but not in knockout mice. In addition, PPARα-null mice displayed reduced lymphocytes and increased monocytes and neutrophils in the blood. Furthermore, PPARα-null mice exhibited increments in the number of total cells (as well as of phenotypically distinct subpopulations of lymph node cells) but also a significant alteration in the number of various subpopulations of splenocytes and thymocytes. Finally, PPARα negatively regulated reactive oxygen species derived by NADPH oxidase in BM-resident progenitor cells. Taken together, our data provide evidence that PPARα is a critical regulator of recruitment, homing, and maturation of BM-derived progenitor cells. Stem Cells 2015;33:1292–1303

Published
2015

13. A novel CD4-CD8α+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis

Author

Sophie Ruiz, Pascal Breton, Isabelle Dimier-Poisson, Daniel Bout, Céline Beauvillain, Philippe Roingeard, and Marie-Noëlle Mévélec

Subjects
0303 health sciences, CD40, Immunology, hemic and immune systems, chemical and pharmacologic phenomena, Spleen, Dendritic cell, Biology, Major histocompatibility complex, Microbiology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Immune system, Antigen, Virology, medicine, biology.protein, Minor histocompatibility antigen, CD80, 030304 developmental biology, 030215 immunology
Abstract

Dendritic cells (DCs) play an essential role in the induction of immune responses to pathogen infections. Native DCs are difficult to obtain in large numbers and consequently the vast majority of DCs employed in all experiments are derived from bone marrow progenitors. In an attempt to solve this problem, we have established a novel CD8alpha(+) DC line (H-2(k)) from spleen, which we have named SRDC line, and which is easy to culture in vitro. These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo. Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression. We report that vaccination with T. gondii antigen-pulsed SRDCs, which synthesize large amounts of interleukin-12, induced protective immune responses against this intracellular pathogen in syngeneic CBA/J mice. This protection was associated with strong cellular and humoral immune responses at systemic and intestinal levels. Spleen and mesenteric lymph node cell proliferations were correlated with a Th1/Th2-type response and a specific SRDC homing to spleen and intestine was observed. The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.

Published
2005

14. Protective Mucosal Th2 Immune Response againstToxoplasma gondiiby Murine Mesenteric Lymph Node Dendritic Cells

Author

Céline Beauvillain, Isabelle Dimier-Poisson, Fleur Aline, Dominique Buzoni-Gatel, Daniel Bout, Marie-Noëlle Mévélec, Immunologie Parasitaire et Vaccinologie, Institut National de la Recherche Agronomique (INRA)-Université de Tours-UMR 483, Inconnu, and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)-UMR 483

Subjects
[SDV]Life Sciences [q-bio], Antibodies, Protozoan, Lymphocyte Activation, Mice, 0302 clinical medicine, Mesentery, Lymph node, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, Adoptive Transfer, Intestinal epithelium, 3. Good health, Intestines, Infectious Diseases, medicine.anatomical_structure, Microbial Immunity and Vaccines, Cytokines, Female, Toxoplasma, Immunology, Antigens, Protozoan, In Vitro Techniques, Microbiology, Immunophenotyping, 03 medical and health sciences, Th2 Cells, Immune system, Antigen, Immunity, parasitic diseases, medicine, Animals, Humans, Immunity, Mucosal, 030304 developmental biology, Toxoplasma gondii, Dendritic Cells, Dendritic cell, Th1 Cells, biology.organism_classification, Mice, Inbred C57BL, Toxoplasmosis, Animal, Immunoglobulin G, Immunoglobulin A, Secretory, Mice, Inbred CBA, Parasitology, Lymph Nodes, Spleen, Ex vivo, 030215 immunology
Abstract

Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response toT. gondii. Despite considerable effort,Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo withT. gondiiantigens (TAg) as a novel investigation approach to vaccination againstT. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosalToxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity toT. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

Published
2003

15. Emergency testing for antineutrophil cytoplasmic antibodies combined with a dialog-based policy between clinician and biologist: effectiveness for the diagnosis of ANCA-associated vasculitis

Author

Alain Chevailler, Jean-François Subra, Jean-François Augusto, Caroline Poli, Céline Beauvillain, François Beloncle, Pierre Antoine Deguigne, and Johnny Sayegh

Subjects
Male, medicine.medical_specialty, Interprofessional Relations, ANCA-Associated Vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Newly diagnosed, Commercial kit, Antibodies, Antineutrophil Cytoplasmic, Time-to-Treatment, immune system diseases, Internal medicine, Internal Medicine, medicine, Humans, cardiovascular diseases, Cooperative Behavior, skin and connective tissue diseases, Anti-neutrophil cytoplasmic antibody, biology, business.industry, Medical record, IIf, Middle Aged, medicine.disease, respiratory tract diseases, Immunology, Emergency Medicine, biology.protein, Female, Antibody, Emergencies, business, Vasculitis
Abstract

A prompt immunosuppressive treatment initiation is crucial in ANCA-associated vasculitis (AAV) to minimize organ injury. The aim of the present work was to analyze the accuracy of emergency ANCA screening to identify rapidly patients with AAV. In our Institution, emergency ANCA screening is based on a telephone call between a Clinician and a Biologist. Indirect immunofluorescence (IIF) for ANCA detection was performed using a commercial kit (Euroimmun(®) Granulocyte Mosaic 12). Positive serums for c- or p-ANCA at IIF are subsequently screened for antigenic specificity (MPO or PR3) by an immunodot technique (immunodot, D-Tek(®).) Positive samples with atypical c- or p-ANCA pattern at IIF are subsequently screened for antigenic specificity by ELISA. Data were retrieved from patients' medical records and confronted to emergency ANCA screening results. Between 2005 and 2012, 114 patients were screened. IIF was positive in 27.2% of patients, but c-/p-ANCA anti-MPO/-PR3 was detected in 13.2% of patients. The sensibility and specificity of IIF combined with immunodot for newly diagnosed AAV were 83.3 and 100%, respectively. Ten patients were newly diagnosed with AAV. In these patients, a specific AAV treatment was initiated less than 24 h following ANCA screening. Emergency ANCA screening based on a clinical gating policy was relevant to identify patients with AAV diagnosis, and was associated with a rapid treatment initiation.

Published
2014

16. Prototypic Long Pentraxin PTX3 Is Present in Breast Milk, Spreads in Tissues, and Protects Neonate Mice from Pseudomonas aeruginosa Lung Infection

Author

Alberto Mantovani, Isabelle Frémaux, Jean François Gauchat, Giuseppe Mancuso, Viorica Cotici, Philippe Descamps, Céline Beauvillain, Angelina Midiri, Concetta Beninati, Cecilia Garlanda, Yves Delneste, Manuela Nebuloni, Pascale Jeannin, Sébastien Jaillon, Yveline Hamon, Barbara Bottazzi, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], University of Messina, Université d'Angers (UA), PRES Université Nantes Angers Le Mans (UNAM), University of Milan, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Università degli Studi di Milano = University of Milan (UNIMI), and Univ Angers, Okina

Subjects
[SDV]Life Sciences [q-bio], Administration, Oral, Lymphocyte Activation, Monocytes, Mice, 0302 clinical medicine, Lactation, Immunology and Allergy, Tissue Distribution, Breast, Receptor, 0303 health sciences, CD11b Antigen, Pattern recognition receptor, PTX3, Acquired immune system, Specific Pathogen-Free Organisms, 3. Good health, [SDV] Life Sciences [q-bio], Serum Amyloid P-Component, Breast Feeding, C-Reactive Protein, medicine.anatomical_structure, Female, Adult, Immunology, Nerve Tissue Proteins, Biology, Breast milk, Cell Line, 03 medical and health sciences, Immune system, Pneumonia, Bacterial, medicine, Animals, Humans, Pseudomonas Infections, 030304 developmental biology, Innate immune system, Milk, Human, Colostrum, Infant, Newborn, Epithelial Cells, Dendritic Cells, Endotoxins, Mice, Inbred C57BL, Animals, Newborn, 030215 immunology
Abstract

Newborns and infants present a higher susceptibility to infection than adults, a vulnerability associated with deficiencies in both the innate and adaptive immune systems. Innate immune receptors are sensors involved in the recognition and elimination of microbes that play a pivotal role at the interface between innate and adaptive immunity. Pentraxin 3 (PTX3), the prototypic long pentraxin, is a soluble pattern recognition receptor involved in the initiation of protective responses against selected pathogens. Because neonates are generally resistant to these pathogens, we suspected that PTX3 may be provided by a maternal source during the early life times. We observed that human colostrum contains high levels of PTX3, and that mammary epithelial cell and CD11b+ milk cells constitutively produce PTX3. Interestingly, PTX3 given orally to neonate mice was rapidly distributed in different organs, and PTX3 ingested during lactation was detected in neonates. Finally, we observed that orally administered PTX3 provided protection against Pseudomonas aeruginosa lung infection in neonate mice. Therefore, breastfeeding constitutes, during the early life times, an important source of PTX3, which actively participates in the protection of neonates against infections. In addition, these results suggest that PTX3 might represent a therapeutic tool for treating neonatal infections and support the view that breastfeeding has beneficial effects on the neonates’ health.

Published
2013

17. The scavenger receptors SRA-1 and SREC-I cooperate with TLR2 in the recognition of the hepatitis C virus non-structural protein 3 by dendritic cells

Author

Vincenzo Barnaba, Simon Blanchard, Mari Scotet, Céline Beauvillain, Ulrich Jarry, Jean-Claude Sirard, Giovanni Magistrelli, Francesca Meloni, Pascale Jeannin, Yves Delneste, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Immunologie et d'Allergologie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Interactions cellulaires et moléculaires des bactéries pathogènes avec l'hôte, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Novimmune SA, This work was supported by institutional grants from Inserm and University of Angers and by grants from the Ligue contre le Cancer (équipe labellisée 2008–2010 and Comité départemental du Maine et Loire), Cancéropole Grand-Ouest and Région Pays de la Loire (project CIMATH). U.J. received a grant from the Association pour la Recherche contre le Cancer., and Sirard, Jean-Claude

Subjects
viruses, Endocytic cycle, Lipopolysaccharide Receptors, MESH: Cricetinae, Hepacivirus, Plasmacytoid dendritic cell, Viral Nonstructural Proteins, MESH: Monocytes, Monocytes, MESH: Recombinant Proteins, Mice, Scavenger receptors, 0302 clinical medicine, MESH: Cricetulus, Interferon, Cricetinae, TLR2, Myeloid Cells, MESH: Animals, MESH: Hepacivirus, Receptors, Scavenger, 0303 health sciences, Toll-like receptor, MESH: Dendritic Cells, MESH: Antigens, CD14, MESH: Bone Marrow Cells, virus diseases, MESH: Toll-Like Receptor 2, Cell Differentiation, Vaccine vector, cooperation between innate receptors, cross-presentation, hcv ns3, scavenger receptors, tlr2, vaccine vector, Endocytosis, Recombinant Proteins, Scavenger Receptors, Class F, 3. Good health, Cell biology, Biochemistry, MESH: Endocytosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug, MESH: Cell Differentiation, [SDV.IMM] Life Sciences [q-bio]/Immunology, Bone Marrow Cells, CHO Cells, Biology, Transfection, 03 medical and health sciences, Cricetulus, MESH: CHO Cells, parasitic diseases, medicine, Animals, Humans, Cooperation between innate receptors, MESH: Receptors, Scavenger, Scavenger receptor, Antigen-presenting cell, MESH: Mice, Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Adaptor Proteins, Signal Transducing, Cross-presentation, MESH: Humans, MESH: Scavenger Receptors, Class F, Hepatology, MESH: Transfection, Dendritic Cells, Dendritic cell, biochemical phenomena, metabolism, and nutrition, MESH: Myeloid Cells, Toll-Like Receptor 2, digestive system diseases, HCV NS3, MESH: Viral Nonstructural Proteins, 030215 immunology
Abstract

International audience; BACKGROUNDS & AIMS: The hepatitis C virus NS3 protein is taken up by myeloid cells in a TLR2-independent manner and activates myeloid cells via TLR2. This study aimed to identify the endocytic receptor(s) involved in the uptake of NS3 by myeloid cells and its relation with TLR2. METHODS: Inhibitors and transfected cells were used to identify the nature of the NS3-binding receptors expressed by myeloid cells. The cooperation between scavenger receptors (SRs) and TLR2 in the NS3-mediated activation of myeloid cells was evaluated using inhibitors, cells from TLR2(-/-) mice, and confocal microscopy. The involvement of SRs in NS3 cross-presentation was evaluated in vitro using an NS3-specific human T-cell clone. RESULTS: We observed that SRs are the main binding structures for NS3 on myeloid cells and identified the SRs SRA-1 and SREC-I as endocytic receptors for NS3. Moreover, both SRs and TLR2 cooperate in NS3-induced myeloid cell activation. CONCLUSION: This study highlights a central role for SRs in NS3 uptake and cross-presentation, and demonstrates a tightly orchestrated cooperation between signalling and endocytic innate receptors in NS3 recognition.

Published
2010

18. Exosomes are an effective vaccine against congenital toxoplasmosis in mice

Author

Céline Beauvillain, Isabelle Dimier-Poisson, Sarah Dion, Josette Pierre, Matthieu O. Juste, Inconnu, Immunologie parasitaire (TOURS UMR IMMUNOLOGIE PARASIT), and Institut National de la Recherche Agronomique (INRA)-Faculte des Sciences Pharmaceutiques

Subjects
Litter Size, Survival, [SDV]Life Sciences [q-bio], Antigens, Protozoan, Toxoplasmosis, Congenital, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Th2 Cells, Antigen, Immunity, Pregnancy, medicine, Animals, Ultrasonics, Central Nervous System Cysts, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, 0303 health sciences, General Veterinary, General Immunology and Microbiology, biology, Vaccination, Public Health, Environmental and Occupational Health, Dendritic Cells, Th1 Cells, medicine.disease, Virology, Toxoplasmosis, 3. Good health, Infectious Diseases, Fertility, Animals, Newborn, Infectious disease (medical specialty), 030220 oncology & carcinogenesis, Immunoglobulin G, Immunology, Antibody Formation, biology.protein, Mice, Inbred CBA, Molecular Medicine, Cytokines, Female, Antibody, Toxoplasma
Abstract

Toxoplasmosis is a serious disease in humans and may cause abortion or congenital infection if a woman is exposed to the disease for the first time during pregnancy. Infection before pregnancy normally results in immunity protecting the foetus, suggesting that it may be possible to block vertical transmission of the parasite by appropriate vaccination before pregnancy. We found that the vaccination of CBA/J mice, before pregnancy, with exosomes secreted by SRDCs pulsed in vitro with Toxoplasma gondii-derived antigens (TAg) induced a protective response in the pups. Indeed, vaccination resulted in the presence of significantly fewer cysts in pup brains. This protection was associated with strong humoral responses in the serum in vivo. We also observed cellular responses in vivo, with cell proliferation associated with the production of cytokines by the splenocytes. Thus, exosomes are nucleic acid-free vesicles able to induce immune responses correlated with protection against T. gondii infection in a congenital model. They are therefore a potentially useful tool for vaccination against infectious disease.

Published
2009

19. Antineutrophil Cytoplasmic Autoantibodies: How Should the Biologist Manage Them?

Author

G Renier, Alain Chevailler, P. Jeannin, J F Subra, Yves Delneste, Céline Beauvillain, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Univ Angers, Okina, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Pathology, medicine.medical_specialty, Anti-nuclear antibody, Neutrophils, Myeloblastin, [SDV]Life Sciences [q-bio], Immunoblotting, Immunology, Enzyme-Linked Immunosorbent Assay, urologic and male genital diseases, Antibodies, Antineutrophil Cytoplasmic, Serology, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, medicine, Internal Medicine, Humans, Immunology and Allergy, cardiovascular diseases, Fluorescent Antibody Technique, Indirect, skin and connective tissue diseases, Peroxidase, 030304 developmental biology, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, 0303 health sciences, biology, business.industry, Panca, Small vessel vasculitis, Autoantibody, Blood Proteins, General Medicine, medicine.disease, biology.organism_classification, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], Allergology, Antineutrophil cytoplasmic antibodies, Microscopic polyangiitis, business, Anti-proteinase 3 antibodies, Antimicrobial Cationic Peptides, Systemic vasculitis, Anti-myeloperoxidase antibodies
Abstract

International audience; Antineutrophil cytoplasmic antibodies (ANCA) are directed against enzymes found in the granules of the polymorphonuclear (PMN) leukocytes. They are detected by indirect immunofluorescence microscopy assays on human ethanol fixed neutrophils. Three different fluorescence patterns can be distinguished: a cytoplasmic pattern (cANCA), a perinuclear pattern (pANCA), and an atypical pattern (aANCA). The use of other fixatives, e.g., formalin and methanol, allows differentiation between the pANCA and the antinuclear antibodies. ANCA specificity is determined by solid phase assays (ELISA, immunodot, and multiplex assay). ANCA with high titres and defined specificities (antiproteinase 3 [PR 3] or antimyeloperoxidase [MPO]) are proven to be good serological markers of active primary systemic vasculitis: c/PR 3-ANCA for Wegener’s granulomatosis and p/MPO-ANCA for microscopic polyangiitis. The former have higher sensitivity and specificity for Wegener’s granulomatosis than the latter for microscopic polyangiitis. ANCA with low titres and unknown specificity have been detected in a wide range of inflammatory and infectious diseases leading to a critical reappraisal of the diagnostic significance of ANCA testing. Physicians must keep in mind the possible occurrence of infectious diseases like subacute endocarditis that could be dramatically worsened by irrelevant immunosuppressive therapy. ANCA findings in certain manifestations, such as the pulmonary-renal syndrome in which massive pulmonary hemorrhage can quickly be life-threatening, warrant ANCA testing as an emergency test for patient care.

Published
2008

20. Neutrophils efficiently cross-prime naive T cells in vivo

Author

Audrey Peres, Yves Delneste, Pierre Guermonprez, Vincenzo Barnaba, Pascale Jeannin, Mari Scotet, Hugues Gascan, Céline Beauvillain, Cytokines : structure, signalisation et prolifération tumorale, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Immunité et cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Inserm Equipe AVENIR, Cancéropôle Grand Ouest, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Beauvillain, Céline

Subjects
Proteasome Endopeptidase Complex, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neutrophils, Ovalbumin, Immunology, Antigen presentation, Bone Marrow Cells, Biology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Biochemistry, 03 medical and health sciences, Mice, 0302 clinical medicine, Cross-Priming, Antigen, MHC class I, Cytotoxic T cell, Animals, Ascitic Fluid, Humans, Antigen-presenting cell, 030304 developmental biology, 0303 health sciences, Antigen Presentation, Cell Biology, Hematology, Natural killer T cell, Flow Cytometry, Molecular biology, 3. Good health, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, ATP-Binding Cassette Transporters, CD8, 030215 immunology
Abstract

Neutrophils are professional phagocytes that migrate early, in high number, to the infection sites. Our study has analyzed how neutrophils cross-present antigens and influence CD8+ T-cell responses. By using highly purified neutrophils from peritoneal exudates and bone marrow, we have shown that neutrophils cross-present ovalbumin to a CD8+ T-cell hybridoma and to naive CD8+ T cells from OT1 transgenic mice. Cross-presentation by neutrophils was TAP and proteasome dependent and was as efficient as in macrophages. Moreover, it actually occurred earlier than in professional antigen-presenting cells. Peritoneal exudate neutrophils from mice injected intraperitoneally with ovalbumin also cross-presented ovalbumin, proving that neutrophils take up and present exogenous antigens into major histocompatibility complex I (MHC I) molecules in vivo. We then evaluated the in vivo influence of antigen cross-presentation by neutrophils on CD8+ T-cell response using β2-microglobulin-deficient mice transferred with OT1 CD8+ T cells and injected with ovalbumin-pulsed neutrophils. Four days after neutrophil injection, OT1 cells proliferated and expressed effector functions (IFN-γ production and cytolysis). They also responded efficiently to a rechallenge with ovalbumin-pulsed dendritic cells in CFA. These data are the first demonstration that neutrophils cross-prime CD8+ T cells in vivo and suggest that they may constitute, together with professional antigen-presenting cells, an attractive target to induce cytotoxic T cells in vaccines.

Published
2007

21. Immunité naturelle : structure et fonction des toll-like receptors

Author

Pascale Jeannin, Céline Beauvillain, Yves Delneste, Cytokines : structure, signalisation et prolifération tumorale, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Inserm Programme AVENIR, Cancéropôle Grand Ouest, Ligue Contre le Cancer, and Beauvillain, Céline

Subjects
0303 health sciences, Toll-like receptor, Innate immune system, [SDV.IMM] Life Sciences [q-bio]/Immunology, Pathogen-associated molecular pattern, Antigen presentation, Innate lymphoid cell, Pattern recognition receptor, General Medicine, Immune receptor, Biology, Acquired immune system, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030304 developmental biology, 030215 immunology
Abstract

International audience; The innate immune system provides the first line of defence against infection. Through a limited number of germline-encoded receptors called pattern recognition receptors (PRRs), innate cells recognize and are activated by highly conserved structures expressed by large group of microorganisms called pathogen-associated molecular patterns (PAMPs). PRRs are involved either in recognition (scavenger receptors, C-type lectins) or in cell activation (Toll-like receptors or TLR, helicases and NOD molecules). TLRs play a pivotal role in cell activation in response to PAMPs. TLR are type I transmembrane proteins characterized by an intracellular Toll/IL 1 receptor homology domain that are expressed by innate immune cells (dendritic cells, macrophages, NK cells), cells of the adaptive immunity (T and B lymphocytes) and non immune cells (epithelial and endothelial cells, fibroblasts). In all the cell types analyzed, TLR agonists, alone or in combination with costimulatory molecules, induce cell activation. The crucial role played by TLR in immune cell activation has been detailed in dendritic cells. A TLR-dependent activation of dendritic cells is required to induce their maturation and migration to regional lymph nodes and to activate naïve T cells. The ability of different cell types to respond to TLR agonists is related to the pattern of expression of the TLRs and its regulation as well as their intracellular localization. Recent studies suggest that the nature of the endocytic and signaling receptors engaged by PAMPs may determine the nature of the immune response generated against the microbial molecules, highlighting the role of TLRs as molecular interfaces between innate and adaptive immunity. In this review are summarized the main biological properties of the TLR molecules.

Published
2007

22. A vaccine based on exosomes secreted by a dendritic cell line confers protection against T. gondii infection in syngeneic and allogeneic mice

Author

Rachel Guiton, Céline Beauvillain, Sophie Ruiz, Daniel Bout, Isabelle Dimier-Poisson, Inconnu, Immunologie Parasitaire et Vaccinologie, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)-UMR 483, and Institut National de la Recherche Agronomique (INRA)-Université de Tours-UMR 483

Subjects
Protozoan Vaccines, Adoptive cell transfer, [SDV]Life Sciences [q-bio], Immunology, Antibodies, Protozoan, Spleen, Antigens, Protozoan, Lymphocyte Activation, Microbiology, Exocytosis, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Antigen, medicine, Animals, Transplantation, Homologous, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Cytoplasmic Vesicles, Dendritic cell, Dendritic Cells, Adoptive Transfer, Microvesicles, 3. Good health, Transplantation, Mice, Inbred C57BL, Transplantation, Isogeneic, Infectious Diseases, medicine.anatomical_structure, Toxoplasmosis, Animal, 030220 oncology & carcinogenesis, biology.protein, Mice, Inbred CBA, Female, Antibody, Toxoplasma
Abstract

Our results show that exosomes secreted by SRDC pulsed in vitro with Toxoplasma gondii-derived antigens (Exo-TAg) induced protective responses against infection with the parasite in both syngeneic and allogeneic mice. After oral infection, syngeneic CBA/J mice exhibited significantly fewer cysts in their brains and allogeneic C57BL/6 mice survived. This protection was associated with strong humoral responses in vivo in serum from both CBA/J and C57BL/6 mice, and with high levels of anti-TAg IgA antibodies in intestinal secretions from CBA/J mice alone. Furthermore, strong cellular responses in vivo were observed in both mouse models. Cellular proliferation was associated with cytokines production by spleen and mesenteric lymph node cells. The results presented here show that exosomes are nucleic acid free vesicles that are able to induce immune responses correlated with protection against parasitic infections in both syngeneic and allogeneic mice. They could constitute an efficient tool for use in vaccination and antitumor strategies based on exosomes.

Published
2007

23. New markers and an old phenomenon: prozone effect disturbing detection of filaggrin (keratin) autoantibodies

Author

Damien Dubois, Gilles Renier, Frederique Dubois-Galopin, Pascale Jeannin, Charles Masson, Céline Beauvillain, Alain Chevailler, and Anne Pillet

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Immunology, Filaggrin Proteins, Biology, Peptides, Cyclic, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, Intermediate Filament Proteins, Rheumatology, Keratin, medicine, Stratum corneum, Humans, Immunology and Allergy, Letters, Fluorescent Antibody Technique, Indirect, Aged, Autoantibodies, Aged, 80 and over, chemistry.chemical_classification, integumentary system, Autoantibody, IIf, Middle Aged, Epithelium, Staining, medicine.anatomical_structure, chemistry, biology.protein, Female, Antibody, Biomarkers, Filaggrin
Abstract

Anti-filaggrin antibodies, also named anti-keratin antibodies (AKA), are serum IgG labelling the stratum corneum of the rat oesophagus epithelium, detectable by indirect immunofluorescence (IIF). They constitute a specific marker for the diagnosis of rheumatoid arthritis (RA).1–3 A laminar staining pattern is seen with most AKA-positive sera (fig 1A), but occasionally the cornified layer is diffusely labelled, and the image also shows foamy staining (fig 1B). Although most authors consider sera as AKA positive only when a linear laminated pattern is observed,4,5 some consider the sera as AKA positive even when the staining is diffuse or foamy.6 Figure 1 Anti-keratin antibodies (AKA) detected by indirect immunofluorescence on rat oesophagus. (A) Typical linear laminated labelling pattern restricted to the upper cornified layer observed in the serum …

Published
2007

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