Descriptor: "MESH: Phagocytosis" - Searchworks@Jio Institute Digital Library Search Results

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82 results on '"MESH: Phagocytosis"'

1. Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation

Author: Amanda Swain, Alexandre Gallerand, Judith C. Sluimer, François Orange, Erik A.L. Biessen, Alexia Castiglione, Inna Gaisler-Salomon, Stefania Carobbio, Laurent Yvan-Charvet, Rodolphe Guinamard, Thierry Berton, Julie Gall, Johanna Merlin, Stephen Rayport, Alexey Sergushichev, Jean-Charles Martin, Marion I. Stunault, Maxim N. Artyomov, Adélie Dumont, Edward B. Thorp, Marion Ayrault, Emmanuel L. Gautier, Justine Masson, Stoyan Ivanov, Pierre Maechler, Nathalie Vaillant, Centre méditerranéen de médecine moléculaire (C3M), 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)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), ITMO University [Russia], Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), The institute of cancer research [London], Université Côte d'Azur (UCA), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-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 Genève = University of Geneva (UNIGE), The Wellcome Trust Sanger Institute [Cambridge], University of Cambridge [UK] (CAM), Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The New York State Psychiatric Institute (NYSPI), Columbia University [New York], University of Haifa [Haifa], Washington University School of Medicine [Saint Louis, MO], Centre Commun de Microscopie Appliquée [Nice] (CCMA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Northwestern University [Chicago, Ill. USA], RWTH Aachen University, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Northwestern University Medical School [Chicago], Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, and Gautier, Emmanuel
Subjects: EXPRESSION, PROMOTES, Endocrinology, Diabetes and Metabolism, Glutamine, [SDV]Life Sciences [q-bio], Cellular detoxification, Oxidative phosphorylation, METABOLISM, MOUSE, Oxidative Phosphorylation, Apoptotic cell clearance, 03 medical and health sciences, Mice, 0302 clinical medicine, MITOCHONDRIA, Phagocytosis, MESH: Oxidative Phosphorylation, Physiology (medical), Internal Medicine, Macrophage, Animals, MESH: Animals, CELL, Efferocytosis, ddc:612, MESH: Phagocytosis, ELECTRON-TRANSPORT, MESH: Mice, Tissue homeostasis, 030304 developmental biology, Amination, MESH: Amination, 0303 health sciences, MESH: Glutamine, Glutaminolysis, Chemistry, Cell Biology, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030217 neurology & neurosurgery
Abstract: Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans. Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.
Published: 2021
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2. Hypoxia Promotes a Mixed Inflammatory-Fibrotic Macrophages Phenotype in Active Sarcoidosis

Author: Florence Jeny, Jean-François Bernaudin, Dominique Valeyre, Marianne Kambouchner, Marina Pretolani, Hilario Nunes, Carole Planès, Valérie Besnard, Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Gestionnaire, Hal Sorbonne Université, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: MESH: Granuloma, MESH: Sarcoidosis, Pulmonary, MESH: NF-kappa B, hypoxia-inducible factor 1, 0302 clinical medicine, MESH: Hypoxia, Fibrosis, Immunology and Allergy, Macrophage, MESH: Phagocytosis, Hypoxia, Cells, Cultured, Original Research, MESH: Cytokines, 0303 health sciences, Granuloma, NF-kappa B, pulmonary sarcoidosis, MESH: Case-Control Studies, Immunohistochemistry, macrophages, 3. Good health, Phenotype, 030220 oncology & carcinogenesis, MESH: Fibrosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, plasminogen activator inhibitor-1, Tumor necrosis factor alpha, Disease Susceptibility, Inflammation Mediators, medicine.symptom, monocytes, MESH: Cells, Cultured, MESH: Sarcoidosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Sarcoidosis, Phagocytosis, MESH: Inflammation Mediators, Immunology, MESH: Disease Susceptibility, MESH: Phenotype, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, Proinflammatory cytokine, Fibroblast migration, 03 medical and health sciences, Immune system, Sarcoidosis, Pulmonary, medicine, Humans, 030304 developmental biology, MESH: Humans, business.industry, fibrosis, MESH: Macrophages, MESH: Immunohistochemistry, Fibroblasts, RC581-607, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, MESH: Fibroblasts, Case-Control Studies, MESH: Biomarkers, Immunologic diseases. Allergy, business, Biomarkers
Abstract: BackgroundMacrophages are pivotal cells in sarcoidosis. Monocytes-derived (MD) macrophages have recently been demonstrated to play a major role especially in pulmonary sarcoidosis. From inflammatory tissues to granulomas, they may be exposed to low oxygen tension environments. As hypoxia impact on sarcoidosis immune cells has never been addressed, we designed the present study to investigate MD-macrophages from sarcoidosis patients in this context. We hypothesized that hypoxia may induce functional changes on MD-macrophages which could have a potential impact on the course of sarcoidosis.MethodsWe studied MD-macrophages, from high active sarcoidosis (AS) (n=26), low active or inactive sarcoidosis (IS) (n=24) and healthy controls (n=34) exposed 24 hours to normoxia (21% O2) or hypoxia (1.5% O2). Different macrophage functions were explored: hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-κB) activation, cytokines secretion, phagocytosis, CD80/CD86/HLA-DR expression, profibrotic response.ResultsWe observed that hypoxia, with a significantly more pronounced effect in AS compared with controls and IS, increased the HIF-1α trans-activity, promoted a proinflammatory response (TNFα, IL1ß) without activating NF-κB pathway and a profibrotic response (TGFß1, PDGF-BB) with PAI-1 secretion associated with human lung fibroblast migration inhibition. These results were confirmed by immunodetection of HIF-1α and PAI-1 in granulomas observed in pulmonary biopsies from patients with sarcoidosis. Hypoxia also decreased the expression of CD80/CD86 and HLA-DR on MD-macrophages in the three groups while it did not impair phagocytosis and the expression of CD36 expression on cells in AS and IS at variance with controls.ConclusionsHypoxia had a significant impact on MD-macrophages from sarcoidosis patients, with the strongest effect seen in patients with high active disease. Therefore, hypoxia could play a significant role in sarcoidosis pathogenesis by increasing the macrophage proinflammatory response, maintaining phagocytosis and reducing antigen presentation, leading to a deficient T cell response. In addition, hypoxia could favor fibrosis by promoting profibrotic cytokines response and by sequestering fibroblasts in the vicinity of granulomas.
Published: 2021
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3. Techno-functional properties and immunomodulatory potential of exopolysaccharide from Lactiplantibacillus plantarum MM89 isolated from human breast milk

Author: Muhammad Shahid Riaz Rajoka, Hafiza Mahreen Mehwish, Haruki Kitazawa, Francisco J. Barba, Laureline Berthelot, Muhammad Umair, Qinchang Zhu, Zhendan He, Liqing Zhao, Tohoku University [Sendai], Shenzhen University [Shenzhen], Universitat de València (UV), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and Le Bihan, Sylvie
Subjects: Immunomodulatory activity, Lactiplantibacillus plantarum, [SDV]Life Sciences [q-bio], Analytical Chemistry, Mice, Phagocytosis, MESH: Lactobacillus plantarum, Animals, Humans, MESH: Animals, MESH: Polysaccharides, Bacterial, MESH: Phagocytosis, MESH: Mice, MESH: Cytokines, MESH: Humans, MESH: Milk, Human, Milk, Human, Polysaccharides, Bacterial, General Medicine, Human breast milk, [SDV] Life Sciences [q-bio], exopolysaccharide, Cytokines, Techno-functional properties, Lactobacillus plantarum, Food Science
Abstract: International audience; An exopolysaccharide, designated as MM89-EPS, was isolated from Lactiplantibacillus plantarum MM89. It was comprised of glucose and mannose molecules with an average molecular weight of 138 kDa. FTIR and NMR spectra showed that MM89-EPS had characteristic polysaccharide functional groups. MM89-EPS displayed excellent water solubility and capacities to retain water and oil due to its porous structure. MM89-EPS exhibited no significant cytotoxicity on RAW264.7 cells and showed strong immunomodulatory activity by increasing phagocytosis, acid phosphatase activity, and cytokine production in RAW264.7 cells. Furthermore, an in vivo study revealed that splenic indices, intestinal IgA levels, serum cytokine levels, and lymphocyte proliferation were increased in an MM89-EPS-treated cyclophosphamide-induced immunosuppressed mouse model. To summarize, our results indicate that MM89-EPS can efficiently enhance the immunostimulatory activity of immune cells and an immunosuppressed mouse model. Hence, MM89-EPS may be use as a potential source of immunomodulatory agent in various food products.
Published: 2022
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4. Pseudomonas aeruginosa utilise ses bactériophages filamenteux pour manipuler la réponse immunitaire

Author: Laurent Debarbieux, Mathieu De Jode, Département de Microbiologie - Department of Microbiology, Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Institut Pasteur [Paris] (IP), and Collège Doctoral
Subjects: MESH: Interferon Type I, Inovirus, [SDV]Life Sciences [q-bio], Virulence, MESH: Virulence, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, medicine, MESH: Animals, MESH: Phagocytosis, MESH: Cell Movement, MESH: Mice, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, MESH: Humans, MESH: Immune System, Pseudomonas aeruginosa, General Medicine, biology.organism_classification, 3. Good health, MESH: Bacterial Physiological Phenomena, MESH: Tumor Necrosis Factor-alpha, MESH: Pseudomonas aeruginosa, MESH: Inovirus, MESH: Bacterial Vaccines, 030215 immunology
Abstract: International audience
Published: 2019
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5. Insights into Streptococcus agalactiae PI-2b pilus biosynthesis and role in adherence to host cells

Author: Cherry Gao, Patrick Trieu-Cuot, Claire Poyart, Bruno Périchon, Julie Guignot, Shaynoor Dramsi, Noémi Szili, Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens (BBPG+), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Barrières et Pathogènes, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the DIM Malinf from the Conseil Régional d’Ile-de-France (Grant DIM130065) to CP and SD and the French Government's Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' Grant ANR-10-LABX-62-IBEID. NS was recipient of a doctoral fellowship from the DIM Malinf., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Cochin (IC UM3 (UMR 8104 / U1016)), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Group B Streptococcus, MESH: Streptococcus agalactiae / physiology, Operon, medicine.disease_cause, Bacterial Adhesion, Pilus, MESH: Adhesins, Bacterial / genetics, S. agalactiae, Cell Wall, Sortase, MESH: Phagocytosis, MESH: Endothelial Cells / microbiology, MESH: Humans Macrophages / microbiology, biology, Infectious Diseases, MESH: Adhesins, Bacterial / metabolism, MESH: Streptococcus agalactiae / pathogenicity, 030106 microbiology, Immunology, education, GBS, Microbiology, Streptococcus agalactiae, THP-1 phagocytosis, 03 medical and health sciences, Phagocytosis, Streptococcal Infections, medicine, PI-2b pilus, Humans, MESH: Streptococcal Infections / microbiology, MESH: Bacterial Adhesion, Adhesins, Bacterial, Gene, Macrophages, MESH: Fimbriae, Bacterial / metabolism, Endothelial Cells, MESH: Cell Wall / metabolism, biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Streptococcus agalactiae / genetics, MESH: Operon / genetics, Bacterial adhesin, 030104 developmental biology, Fimbriae, Bacterial, Pilin, biology.protein, bacteria, Biogenesis
Abstract: International audience; The core PI-2b pilus present in "hypervirulent" ST-17 Streptococcus agalactiae strains consists of three pilin subunits (Spb1, Ap1 and Ap2) assembled by sortase SrtC1 and cell-wall anchored by Srt2. Spb1 was shown to be the major pilin and Ap2 the anchor pilin. Ap1 is a putative adhesin. Two additional genes, orf and lep, are part of this operon. The contribution of Lep and Ap1 to the biogenesis of the PI-2b pilus was investigated. Concerning the role of PI-2b, we found that higher PI-2b expression resulted in higher adherence to human brain endothelial cells and higher phagocytosis by human THP1 macrophages.
Published: 2019
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6. Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins

Author: Michel Monod, Oumaïma Ibrahim-Granet, Rajashri Shende, Rémi Beau, Jean-Paul Latgé, Karl-Heinz Gührs, Taruna Madan, Jayanta K. Pal, Arvind Sahu, Vishukumar Aimanianda, Sarah Sze Wah Wong, Srikanth Rapole, Savitribai Phule Pune University [Pune, india], Aspergillus, Institut Pasteur [Paris], Cytokines et Inflammation, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, National Institute for Research in Reproductive Health [Mumbai, India] (ICMR), This work was supported in part by a bilateral COMASPIN grant from the Department of Science and Technology (DST) India and l'Agence Nationale de la Recherché (ANR) France, and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, metalloprotease, [SDV]Life Sciences [q-bio], Host Defense Mechanism, Biochemistry, MESH: Mice, Knockout, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Aspergillus fumigatus, MESH: Lectins, MESH: Collagen, complement, MESH: Animals, MESH: Immune Evasion, MESH: Phagocytosis, biology, Chemistry, phagocytosis, MESH: Complement C3, MESH: Complement C4, MESH: Gene Expression Regulation, Antibody opsonization, Aspergillus, MESH: Complement C5, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, MESH: Fungal Proteins, MESH: Aspergillus fumigatus, Proteases, MESH: Invasive Pulmonary Aspergillosis, infectious disease, Immunology, MESH: Mice, Inbred BALB C, MESH: Metalloendopeptidases, Microbiology, 03 medical and health sciences, Immune system, MESH: Spores, Fungal, MESH: Lung, Molecular Biology, MESH: Mice, complement system, immune evasion, Innate immune system, MESH: Humans, MESH: Host-Pathogen Interactions, C4A, MESH: Macrophages, Cell Biology, biology.organism_classification, MESH: Male, Complement system, 030104 developmental biology, MESH: Mannose-Binding Protein-Associated Serine Proteases, inflammation, MESH: Disease Models, Animal
Abstract: International audience; Innate immunity in animals including humans encompasses the complement system, which is considered an important host defense mechanism against Aspergillus fumigatus, one of the most ubiquitous opportunistic human fungal pathogens. Previously, it has been shown that the alkaline protease Alp1p secreted from A. fumigatus mycelia degrades the complement components C3, C4, and C5. However, it remains unclear how the fungal spores (i.e. conidia) defend themselves against the activities of the complement system immediately after inhalation into the lung. Here, we show that A. fumigatus conidia contain a metalloprotease Mep1p, which is released upon conidial contact with collagen and inactivates all three complement pathways. In particular, Mep1p efficiently inactivated the major complement components C3, C4, and C5 and their activation products (C3a, C4a, and C5a) as well as the pattern-recognition molecules MBL and ficolin-1, either by directly cleaving them or by cleaving them to a form that is further broken down by other proteases of the complement system. Moreover, incubation of Mep1p with human serum significantly inhibited the complement hemolytic activity and conidial opsonization by C3b and their subsequent phagocytosis by macrophages. Together, these results indicate that Mep1p associated with and released from A. fumigatus conidia likely facilitates early immune evasion by disarming the complement defense in the human host.
Published: 2018
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7. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals

Author: Joaquín Ariño, Nuria Trevijano-Contador, Oscar Zaragoza, Suélen Andreia Rossi, Guilhem Janbon, Haroldo Cesar de Oliveira, Ángel Zaballos, Irene Llorente, Rocío García-Rodas, National Centre for Microbiology [Madrid], Instituto de Salud Carlos III [Madrid] (ISC), Faculdade de Ciências Farmacêuticas [São Paulo, Brazil], Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris], Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona (UAB), Departament de Bioquímica i Biologia Molecular, OZ is funded by grant SAF2014-54336-R and SAF2017-86192-R1 from the Spanish Ministry for Economics, Industry and Competitivity. JA is funded by grants BFU2014-54591-C2-1-P and BFU2017-82574-P (Spanish Ministry for Economics, Industry and Competitivity) and an 'Ajut 2014SGR-4' (Generalitat de Catalunya). NT-C was supported by a FPI fellowship (reference BES-2012-051837). SAR was supported by a fellowship from Coordenação de aperfeiçoamento de pessoal de nivel superior, CAPES, program Ciências Sem Fronteiras (202436/2015-2). HCdO is funded by postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-BEPE 2016/20631-3). RG-R is funded by a 'Juan de la Cierva' Contract from the Spanish Ministry for Economics, Industry and Competitivity (reference: IJCI-2015-25683)., We want to thank Dr. Joseph Heitman (Duke University Medical Center, Durham, North Carolina, United States of America), Dr. Robin May (Birmingham University, UK) and Dr. June Kwon-Chung (NIH, Bethesda, USA), for the gift of strains. I.L. participated in this work in the frame of the master in 'Microbiology Applied to Public Health and Research on Infectious Diseases' (Alcalá University and Instituto de Salud Carlos III). We would like to thank Pilar Jiménez Sancho (Genomics Unit, Core Scientific Services, Instituto de Salud Carlos III) for her technical assistance in the RNAseq experiments. We also would like to thank Dr. Manuel Lombardía (Proteomics Facility, National Centre for Biotechnology, Madrid, Spain), for his technical assistance in peptide synthesis., Institut Pasteur [Paris] (IP), Ministerio de Economía y Competitividad (España), Government of Catalonia (España), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Fundação de Amparo à Pesquisa do Estado de São Paulo (Brasil), Ministerio de Economía, Industria y Competitividad (España), Instituto de Salud Carlos III, Universidade Estadual Paulista (Unesp), Département de Mycologie, Universitat Autònoma de Barcelona, and Albert Einstein College of Medicine
Subjects: 0301 basic medicine, Male, MESH: Signal Transduction, Cell, MESH: Quorum Sensing, Mice, Gene expression, MESH: RAW 264.7 Cells, MESH: Animals, Biology (General), MESH: Phagocytosis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, Chemistry, Quorum Sensing, Cryptococcosis, MESH: Host-Pathogen Interactions / physiology, MESH: Cryptococcosis / microbiology, 3. Good health, Cell biology, medicine.anatomical_structure, Phenotype, Host-Pathogen Interactions, Signal transduction, Physiological parameters, Signal Transduction, MESH: Cryptococcus neoformans / cytology, MESH: Host-Pathogen Interactions / genetics, QH301-705.5, 030106 microbiology, Immunology, Genes, Fungal, MESH: Phenotype, Microbiology, Models, Biological, 03 medical and health sciences, MESH: Gene Expression Profiling, Phagocytosis, MESH: Mice, Inbred C57BL, Virology, Calnexin, Genetics, medicine, Animals, Humans, MESH: Macrophages / microbiology, Molecular Biology, MESH: Mice, Protein kinase C, Cryptococcus neoformans, MESH: Humans, Gene Expression Profiling, Macrophages, MESH: Cryptococcus neoformans / pathogenicity, MESH: Models, Biological, Metabolism, MESH: Cryptococcus neoformans / genetics, RC581-607, biology.organism_classification, In vitro, MESH: Male, Mice, Inbred C57BL, Cryptococcus, RAW 264.7 Cells, Carbon dioxide, Parasitology, Cell formation, Immunologic diseases. Allergy, MESH: Genes, Fungal
Abstract: Made available in DSpace on 2018-12-11T17:20:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-01 Agència de Gestió d’Ajuts Universitaris i de Recerca Secretaría de Estado de Investigación, Desarrollo e Innovación Dirección General de Investigación Científica y Técnica Cryptococcus neoformans is an encapsulated pathogenic yeast that can change the size of the cells during infection. In particular, this process can occur by enlarging the size of the capsule without modifying the size of the cell body, or by increasing the diameter of the cell body, which is normally accompanied by an increase of the capsule too. This last process leads to the formation of cells of an abnormal enlarged size denominated titan cells. Previous works characterized titan cell formation during pulmonary infection but research on this topic has been hampered due to the difficulty to obtain them in vitro. In this work, we describe in vitro conditions (low nutrient, serum supplemented medium at neutral pH) that promote the transition from regular to titan-like cells. Moreover, addition of azide and static incubation of the cultures in a CO2enriched atmosphere favored cellular enlargement. This transition occurred at low cell densities, suggesting that the process was regulated by quorum sensing molecules and it was independent of the cryptococcal serotype/species. Transition to titan-like cell was impaired by pharmacological inhibition of PKC signaling pathway. Analysis of the gene expression profile during the transition to titan-like cells showed overexpression of enzymes involved in carbohydrate metabolism, as well as proteins from the coatomer complex, and related to iron metabolism. Indeed, we observed that iron limitation also induced the formation of titan cells. Our gene expression analysis also revealed other elements involved in titan cell formation, such as calnexin, whose absence resulted in appearance of abnormal large cells even in regular rich media. In summary, our work provides a new alternative method to investigate titan cell formation devoid the bioethical problems that involve animal experimentation. Mycology Reference Laboratory National Centre for Microbiology Instituto de Salud Carlos III, Majadahonda Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas Laboratório de Micologia Clínica Genomics Unit Core Scientific Services Instituto de Salud Carlos III, Majadahonda Institut Pasteur Unité Biologie des ARN des Pathogènes Fongiques Département de Mycologie Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de Barcelona Albert Einstein College of Medicine Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas Laboratório de Micologia Clínica Agència de Gestió d’Ajuts Universitaris i de Recerca: 2014SGR-4 Secretaría de Estado de Investigación, Desarrollo e Innovación: BFU2014-54591-C2-1-P Dirección General de Investigación Científica y Técnica: BFU2017-82574-P Secretaría de Estado de Investigación, Desarrollo e Innovación: SAF2014-54336-R Dirección General de Investigación Científica y Técnica: SAF2017-86192-R
Published: 2018
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8. Absence of Fungal Spore Internalization by Bronchial Epithelium in Mouse Models Evidenced by a New Bioimaging Approach and Transmission Electronic Microscopy

Author: Jean-Christophe Olivo-Marin, Dea Garcia-Hermoso, Fabrice de Chaumont, Charlotte Renaudat, Stéphane Bretagne, Grégory Jouvion, Fabrice Chrétien, Blandine Rammaert, Claire Szczepaniak, Françoise Dromer, CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Analyse d'Images biologiques, Centre Imagerie Cellulaire Santé (CICS), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre Hospitalier Sainte Anne [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Supported by the Prix de la Chancellerie des Universités de Paris, LegsPoix and the Institut Pasteur (Program de Recherche transversal, PTR 409).B.R. is recipient of Institut Pasteur, Ecole Polytechnique, Arts et MetiersParisTech, École supérieure de physique et de chimie industrielles de laville de Paris (ESPCI Paris Tech), Université de technologie de Compiégne(UTC), Commissariat á l’énergie atomique et aux énergies alternatives(CEA), CNRS, Labex BioPsy, and AP-HP fellowships., We thank Huot Khun for technical assistance with histology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: MESH: Sordariales, Male, MESH: Sequence Analysis, DNA, Pathology, Cell Membrane Permeability, Lichtheimia corymbifera, MESH: Molecular Diagnostic Techniques, Aspergillosis, Epithelium, Aspergillus fumigatus, Mice, MESH: Animals, MESH: Cell Membrane Permeability, MESH: Phagocytosis, Internalization, Lung, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Treatment Outcome, media_common, MESH: Middle Aged, biology, Spores, Fungal, respiratory system, medicine.anatomical_structure, MESH: Young Adult, MESH: Epithelial Cells, MESH: Survival Analysis, MESH: Microscopy, Electron, Transmission, MESH: Aspergillus fumigatus, medicine.medical_specialty, media_common.quotation_subject, Phagocytosis, Pathology and Forensic Medicine, MESH: Mycoses, Microscopy, Electron, Transmission, MESH: Spores, Fungal, medicine, Animals, Humans, MESH: Lung, MESH: Aspergillosis, MESH: Mice, MESH: Humans, fungi, Epithelial Cells, medicine.disease, biology.organism_classification, MESH: Male, respiratory tract diseases, Spore, MESH: Epithelium, Disease Models, Animal, MESH: Disease Models, Animal
Abstract: International audience; Clinical data and experimental studies suggest that bronchial epithelium could serve as a portal of entry for invasive fungal infections. We therefore analyzed the interactions between molds and the bronchial/bronchiolar epithelium at the early steps after inhalation. We developed invasive aspergillosis (Aspergillus fumigatus) and mucormycosis (Lichtheimia corymbifera) murine models that mimic the main clinical risk factors for these infections. Histopathology studies were completed with a specific computer-assisted morphometric method to quantify bronchial and alveolar spores and with transmission electron microscopy. Morphometric analysis revealed a higher number of bronchial/bronchiolar spores for A. fumigatus than L. corymbifera. The bronchial/bronchiolar spores decreased between 1 and 18 hours after inoculation for both fungi, except in corticosteroid-treated mice infected with A. fumigatus, suggesting an effect of cortisone on bronchial spore clearance. No increase in the number of spores of any species was observed over time at the basal pole of the epithelium, suggesting the lack of transepithelial crossing. Transmission electron microscopy did not show spore internalization by bronchial epithelial cells. Instead, spores were phagocytized by mononuclear cells on the apical pole of epithelial cells. Early epithelial internalization of fungal spores in vivo cannot explain the bronchial/bronchiolar epithelium invasion observed in some invasive mold infections. The bioimaging approach provides a useful means to accurately enumerate and localize the fungal spores in the pulmonary tissues.
Published: 2015
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9. Staphylococcus aureus Adenosine Inhibits sPLA2-IIA–Mediated Host Killing in the Airways

Author: Jérémy Brunet, Erwan Pernet, Lhousseine Touqui, Laurent Guillemot, Michel Chignard, Yongzheng Wu, Défense innée et inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by Domaine d’Intérêts Majeur-Maladies Infectieuses from the Région Ile de France (a Ph.D. fellowship to E.P.) and Vaincre la Mucoviscidose Grants RF20120600672 and RF20130500830 (to Y.W.)., We thank Dr. D. Missiakas (University of Chicago, Chicago, IL) for providing the S. aureus Newman WT, ∆adsA mutant, and AdsA complemented strains, and Dr. Tarek Msadek (Institut Pasteur, Paris, France) for the different WT strains of S. aureus., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Wu, Yongzheng
Subjects: Male, Adenosine, MESH: Macrophages, Alveolar, Pyridines, Mutant, Nod2 Signaling Adaptor Protein, MESH: NF-kappa B, MESH: Cricetinae, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, MESH: Cricetulus, Cricetinae, MESH: Staphylococcus aureus, MESH: Nod2 Signaling Adaptor Protein, Immunology and Allergy, MESH: Animals, Phosphorylation, MESH: Phagocytosis, 0303 health sciences, Imidazoles, NF-kappa B, Staphylococcal Infections, MESH: Group II Phospholipases A2, 3. Good health, Staphylococcus aureus, Host-Pathogen Interactions, MESH: Receptor, Adenosine A2A, MESH: Receptor, Adenosine A2B, Bronchoalveolar Lavage Fluid, MESH: Imidazoles, medicine.drug, Receptor, Adenosine A2A, Phagocytosis, p38 mitogen-activated protein kinases, Guinea Pigs, Immunology, MESH: Staphylococcal Infections, CHO Cells, MESH: Cyclic AMP-Dependent Protein Kinases, Biology, Receptor, Adenosine A2B, Group II Phospholipases A2, Cell Line, MESH: Guinea Pigs, Microbiology, 03 medical and health sciences, Cricetulus, MESH: CHO Cells, Macrophages, Alveolar, medicine, Animals, Protein kinase A, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, MESH: Phosphorylation, MESH: Bronchoalveolar Lavage Fluid, MESH: Host-Pathogen Interactions, MESH: Pyridines, MESH: Adenosine, Cyclic AMP-Dependent Protein Kinases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Adenosine receptor, MESH: Male, MESH: Cell Line, MESH: p38 Mitogen-Activated Protein Kinases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030215 immunology
Abstract: Staphylococcus aureus is a common cause of bacterial infections in respiratory diseases. It secretes molecules to dampen host immunity, and the recently identified adenosine is one of these molecules. The type IIA secretory phospholipase A2 (sPLA2-IIA) is a host protein endowed with antibacterial properties, especially against Gram-positive bacteria such as S. aureus. However, the role of adenosine in sPLA2-IIA–mediated S. aureus killing by host is still unknown. The present studies showed that the S. aureus mutant lacking adenosine production (∆adsA strain) increased sPLA2-IIA expression in guinea pig airways and was cleared more efficiently, compared with the wild-type strain. S. aureus ∆adsA strain induced sPLA2-IIA expression by alveolar macrophages after phagocytic process via NOD2–NF-κB–dependent mechanism. However, S. aureus adenosine (wild-type and adsA-complemented strains) and exogenous adenosine downregulated S. aureus phagocytosis by alveolar macrophages, leading to inhibition of sPLA2-IIA expression. This occurred through inhibition of p38 phosphorylation via adenosine receptors A2a-, A2b-, and protein kinase A–dependent pathways. Taken together, our studies suggest that, in the airway, S. aureus escapes sPLA2-IIA–mediated killing through adenosine-mediated inhibition of phagocytosis and sPLA2-IIA expression.
Published: 2015
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10. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author: Bianca Balbino, George Delidakis, Tae Hyun Kang, Makiko Watanabe, Kendra Triplett, Anja Lux, Navin Varadarajan, Odile Richard-Le Goff, Oana I. Lungu, Pierre Bruhns, George Georgiou, Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Wissam Charab, Falk Nimmerjahn, Yan Jessie Zhang, Hidetaka Tanno, Wupeng Yan, Nicholas M. Marshall, Moses Donkor, Chang-Han Lee, Jiwon Lee, Ronald P. Taylor, Biliana Todorova, University of Texas at Austin [Austin], University of Houston, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Erlangen-Nürnberg [Germany], University of Virginia School of Medicine [US], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), University of Virginia, Department of Biochemistry and Molecular Genetics (xxx), University of Virginia [Charlottesville], We thank Y. Tanno for assistance with protein expression, A. Bui for assistance with liquid chromatography–tandem mass spectrometry, P. Tucker (University of Texas at Austin) for cancer cell lines, D. Lee (MD Anderson Cancer Center) for patient-derived primary acute lymphocytic leukemia cells, the Macromolecular Crystallography Facility of the University of Texas at Austin, the Berkeley Center for Structural Biology, the Advanced Light Source (supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract DE-AC02-05CH11231), the Proteomics Facility at the University of Texas at Austin (supported by grant RP110782 from the Cancer Prevention Research Training Program), and A. Nicola and the Plate-Forme d'Imagerie Dynamique (Institut Pasteur, Paris) for help with the bioluminescence experiments. Supported by the Clayton Foundation, the Institut Pasteur (P.B. laboratory), the Institut National de la Santé et de la Recherche Médicale (P.B. laboratory), the European Research Council Seventh Frame-work Program (ERC-2013-CoG 616050 for the P.B. laboratory), the Pasteur–Paris University International PhD program (B.B.), the Cancer Prevention Research Training Program (RP140108 to M.D., RP160015 to H.T., and RP130570 to N.V.), the American Cancer Society (123506-PF-13-354-01-CDD to N.M.), Uehara Memorial Foundation (H.T.), Japan Society for the Promotion of Science (H.T.), Deutsche Forschungsgemeinschaft (CRC1181-A07 to F.N.), the US National Institutes of Health (R01CA174385 to N.V., and R01 GM104896 to Y.J.Z.) and the Welch Foundation (F-1778 to Y.J.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Cancer Prevention and Research Institute of Texas., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Martin, Marie, and Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID
Subjects: Cytotoxicity, Immunologic, 0301 basic medicine, Cellular immunity, MESH: Complement C1q, MESH: Immunotherapy, Crystallography, X-Ray, Mass Spectrometry, MESH: Antibodies, Monoclonal, Mice, Tandem Mass Spectrometry, Neoplasms, Immunology and Allergy, MESH: Animals, MESH: Neoplasms, Cytotoxicity, Receptor, MESH: Phagocytosis, MESH: Crystallization, MESH: Immunoglobulin G, biology, Effector, Antibodies, Monoclonal, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Chromatography, Gel, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, 3. Good health, Cell biology, MESH: Surface Plasmon Resonance, Chromatography, Gel, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Antibody, Crystallization, Lymphoma, B-Cell, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Enzyme-Linked Immunosorbent Assay, In Vitro Techniques, MESH: Receptors, IgG, MESH: Immunoglobulin Fc Fragments, 03 medical and health sciences, Classical complement pathway, Immune system, Phagocytosis, Cell Line, Tumor, Animals, Humans, MESH: Cytotoxicity, Immunologic, MESH: Mice, MESH: Lymphoma, B-Cell, MESH: In Vitro Techniques, MESH: Mass Spectrometry, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, Complement C1q, Receptors, IgG, MESH: Tandem Mass Spectrometry, Surface Plasmon Resonance, MESH: Crystallography, X-Ray, Immunoglobulin Fc Fragments, Complement system, MESH: Burkitt Lymphoma, 030104 developmental biology, Immunoglobulin G, biology.protein, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Chromatography, Liquid, Chromatography, Liquid
Abstract: International audience; Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.
Published: 2017
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11. Pseudomonas aeruginosa Exolysin promotes bacterial growth in lungs, alveolar damage and bacterial dissemination

Author: François Cretin, Guillaume Golovkine, Emmanuel Lemichez, Philippe Huber, Benoit Gallet, Stéphanie Bouillot, Patrick Munro, Ina Attree, Guy Schoehn, Emeline Reboud, Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), This work was supported by institutional grants from the Commissariat à l’Energie Atomique, the Institut National de la Santé Et de la Recherche Médicale, the Université Grenoble-Alpes and the Centre National de la Recherche Scientifique, as well as the Laboratoire d’Excellence GRAL [grant number ANR-10-LABX-49-01 to ER] and SIGNALIFE [grant number ANR-11-LABX-28-01], Agence National de la Recherche [ANR-15-CE11-0018-01]. This work used the platforms of the Grenoble Instruct centre (ISBG, UMS 3518 CNRS-CEA-UJF-EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB). The electron microscope facility is supported by the Rhône-Alpes Region, the Fondation Recherche Medicale (FRM), the fonds FEDER, the Centre National de la Recherche Scientifique (CNRS), the Commissariat à l’Energie Atomique, the University of Grenoble, EMBL, and the GIS-Infrastrutures en Biologie Sante et Agronomie (IBISA)., Grenoble Instruct-ERIC Center (ISBG : UMS 3518 CNRS-CEA-UGA-EMBL), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-15-CE11-0018,HemoPseudo,Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence(2015), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), Université Grenoble Alpes, Inserm, CEA, BIG-Biologie du Cancer et de l’Infection, Grenoble, France, Huber, Philippe, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence - - HemoPseudo2015 - ANR-15-CE11-0018 - AAPG2015 - VALID, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, 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)-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0301 basic medicine, Pore Forming Cytotoxic Proteins, Science, medicine.medical_treatment, Phagocytosis, Bacterial Toxins, MESH: Mice, Inbred BALB C, Bacteremia, Biology, medicine.disease_cause, MESH: Alveolar Epithelial Cells, Virulence factor, Article, Microbiology, Type three secretion system, 03 medical and health sciences, Mice, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Animals, MESH: Animals, MESH: Bacteremia, MESH: Phagocytosis, MESH: Mice, Mice, Inbred BALB C, Multidisciplinary, Lung, MESH: Pore Forming Cytotoxic Proteins, Pseudomonas aeruginosa, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Cytokine, medicine.anatomical_structure, MESH: Bacterial Toxins, Alveolar Epithelial Cells, MESH: Pseudomonas aeruginosa, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Ectopic expression, Female, MESH: Female
Abstract: Exolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of Pseudomonas aeruginosa strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an exlA-negative strain induced similar tissue injuries. In addition, ExlA conferred on bacteria the capacity to proliferate in lungs and to disseminate in secondary organs, similar to bacteria possessing a functional T3SS. CLJ1 did not promote a strong neutrophil infiltration in the alveoli, owing to the weak pro-inflammatory cytokine reaction engendered by the strain. However, CLJ1 was rapidly eliminated from the blood in a bacteremia model, suggesting that it can be promptly phagocytosed by immune cells. Together, our study ascribes to ExlA-secreting bacteria the capacity to proliferate in the lung and to damage pulmonary tissues, thereby promoting metastatic infections, in absence of substantial immune response exacerbation.
Published: 2017
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12. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

Author: Bernard Bonnotte, Annemieke G. Laarhoven, Kim Santegoets, Philippe Saas, Maxime Samson, Gestur Vidarsson, Sylvain Audia, Olivier Facy, Timothy R D J Radstake, Pablo Ortega-Deballon, Nona Janikashvili, Laboratory of Translational Immunology [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Sanquin Research, University of Amsterdam [Amsterdam] (UvA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), 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]), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Landsteiner Laboratory, University Medical Center Utrecht [the Netherlands] ( UMC Utrecht ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), University of Amsterdam [Amsterdam] ( UvA ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Male, MESH: Spleen, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], MESH : Aged, MESH: Flow Cytometry, Immunoglobulin G, 0302 clinical medicine, MESH : Antigens, CD86, MESH: Autoimmune Diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, CD86, MESH: Immunoglobulins, Intravenous, MESH : Receptors, IgG, MESH : Macrophages, MESH: Immunoglobulin G, MESH: Middle Aged, Immunoglobulins, Intravenous, Flow Cytometry, macrophages, MESH : Phenotype, Splenectomy, Antibody, IgG, Phagocytosis, Immunology, Immunoglobulins, Spleen, MESH: Receptors, IgG, MESH: Phenotype, MESH: Splenectomy, 03 medical and health sciences, MESH : Autoimmune Diseases, Genetic, MESH: Polymorphism, Genetic, Humans, MESH : Middle Aged, Polymorphism, Aged, Polymorphism, Genetic, MESH: Humans, Macrophages, MESH : Humans, MESH: Adult, 030104 developmental biology, spleen, B7-2 Antigen, MESH: Female, 0301 basic medicine, MESH : Polymorphism, Genetic, Receptor expression, medicine.disease_cause, Autoimmunity, immune system diseases, hemic and lymphatic diseases, Receptors, Immunology and Allergy, MESH : Female, MESH: Phagocytosis, MESH: Aged, biology, MESH : Thrombocytopenia, Fc receptors, autoimmunity, MESH : Adult, Middle Aged, Antigens, CD86, medicine.anatomical_structure, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Immunoglobulins, Intravenous, Intravenous, MESH : Spleen, Adult, MESH : Immunoglobulin G, MESH : Flow Cytometry, MESH : Male, chemical and pharmacologic phenomena, MESH: Antigens, CD86, Autoimmune Diseases, All institutes and research themes of the Radboud University Medical Center, MESH : Phagocytosis, medicine, Journal Article, Antigens, Opsonin, MESH : Splenectomy, MESH: Thrombocytopenia, Receptors, IgG, MESH: Macrophages, Original Articles, Thrombocytopenia, MESH: Male, biology.protein, 030215 immunology
Abstract: Summary Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.
Published: 2017
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13. Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells

Author: Sandra Cortès, Marie José Stasia, Jean-Luc Lenormand, Julie Brault, Guillaume Vaganay, Aline Le Roy, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Synthelis, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0301 basic medicine, Pharmaceutical Science, chronic granulomatous disease, Granulomatous Disease, Chronic, law.invention, Cell membrane, chemistry.chemical_compound, Chronic granulomatous disease, MESH: Granulomatous Disease, Chronic, International Journal of Nanomedicine, NADPH oxidase complex, law, protein therapy, Drug Discovery, MESH: Phagocytosis, Candida, Original Research, Oxidase test, NADPH oxidase, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, MESH: Reactive Oxygen Species, Cell Differentiation, Genetic Diseases, X-Linked, General Medicine, MESH: Protein Subunits, 3. Good health, medicine.anatomical_structure, Child, Preschool, Recombinant DNA, Nicotinamide adenine dinucleotide phosphate, MESH: Proteolipids, MESH: Cell Differentiation, induced pluripotent stem cells, Proteolipids, Biophysics, Bioengineering, MESH: Induced Pluripotent Stem Cells, MESH: NADPH Oxidases, Biomaterials, 03 medical and health sciences, Phagocytosis, proteoliposomes, MESH: Candida, MESH: Genetic Diseases, X-Linked, medicine, Humans, MESH: Humans, Macrophages, MESH: Child, Preschool, Organic Chemistry, Cell Membrane, MESH: Macrophages, NADPH Oxidases, medicine.disease, Molecular biology, Protein Subunits, 030104 developmental biology, chemistry, Membrane protein, Immunology, biology.protein, Reactive Oxygen Species, MESH: Cell Membrane
Abstract: Julie Brault,1,2 Guillaume Vaganay,3 Aline Le Roy,4–6 Jean-Luc Lenormand,1 Sandra Cortes,3 Marie José Stasia1,2 1UMR CNRS 5525, University of Grenoble Alpes, Grenoble, France; 2CGD Diagnosis and Research Centre, University Hospital Centre of Grenoble Alpes, Grenoble, France; 3Synthelis SAS, La Tronche, France; 4IBS, University of Grenoble Alpes, Grenoble, France; 5CNRS, IBS, University Grenoble Alpes, Grenoble, France; 6CEA, IBS, University of Grenoble Alpes, Grenoble, France Abstract: Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency due to dysfunction of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex leading to severe and recurrent infections in early childhood. The main genetic form is the X-linked CGD leading to the absence of cytochrome b558 composed of NOX2 and p22phox, the membrane partners of the NADPH oxidase complex. The first cause of death of CGD patients is pulmonary infections. Recombinant proteoliposome-based therapy is an emerging and innovative approach for membrane protein delivery, which could be an alternative local, targeted treatment to fight lung infections in CGD patients. We developed an enzyme therapy using recombinant NOX2/p22phox liposomes to supply the NADPH oxidase activity in X0-linked CGD (X0-CGD) macrophages. Using an optimized prokaryotic cell-free protein synthesis system, a recombinant cytochrome b558 containing functional hemes was produced and directly inserted into the lipid bilayer of specific liposomes. The size of the NOX2/p22phox liposomes was estimated to be around 700nm. These proteoliposomes were able to generate reactive oxygen species (ROS) in an activated reconstituted cell-free NADPH oxidase activation assay in the presence of recombinant p47phox, p67phox and Rac, the cytosolic components of the NADPH oxidase complex. Furthermore, using flow cytometry and fluorescence microscopy, we demonstrated that cytochrome b558 was successfully delivered to the plasma membrane of X0-CGD-induced pluripotent stem cell (iPSC)-derived macrophages. In addition, NADPH oxidase activity was restored in X0-CGD iPSC-derived macrophages treated with NOX2/p22phox liposomes for 8h without any toxicity. In conclusion, we confirmed that proteoliposomes provide a new promising technology for the delivery of functional proteins to the membrane of targeted cells. This efficient liposomal enzyme replacement therapy will be useful for future treatment of pulmonary infections in CGD patients refractory to conventional anti-infectious treatments. Keywords: protein therapy, proteoliposomes, chronic granulomatous disease, NADPH oxidase, induced pluripotent stem cells, macrophages&nbsp
Published: 2017
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14. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions

Author: Giulio Superti-Furga, Anna-Dorothea Gorki, Philipp Starkl, Stefan Kubicek, Keiryn L. Bennett, Michael C. Aichinger, Kilian Huber, Branka Radic-Sarikas, Rui Martins, Kari Vaahtomeri, Dontscho Kerjaschki, Ana Korosec, Omar Sharif, Thomas Decker, Stephanie C. Eisenbarth, Michael Sixt, Markus Brown, Harald Esterbauer, Sylvia Knapp, Riem Gawish, Jacques Colinge, Michelle Duggan, Karin Lakovits, Federica Quattrone, Charles-Hugues Lardeau, Simona Saluzzo, Anastasiya Hladik, Julia Maier, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Phagocyte, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, MESH: Gram-Negative Bacterial Infections, Immunology and Allergy, Guanine Nucleotide Exchange Factors, MESH: RAW 264.7 Cells, MESH: Guanine Nucleotide Exchange Factors, MESH: Animals, MESH: Immune Evasion, Cytoskeleton, cdc42 GTP-Binding Protein, MESH: Phagocytosis, Heme, MESH: Sepsis, Mice, Knockout, Quinine, MESH: Heme Oxygenase-1, MESH: Hemolysis, Hemolysis, 3. Good health, Anti-Bacterial Agents, medicine.anatomical_structure, MESH: Heme, Female, Guanine nucleotide exchange factor, MESH: Membrane Proteins, Dock8, MESH: Quinine, Phagocytosis, Immunology, Microbiology, Sepsis, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Anti-Bacterial Agents, medicine, MESH: Cytoskeleton, Animals, Humans, MESH: Mice, Immune Evasion, MESH: cdc42 GTP-Binding Protein, MESH: Humans, Macrophages, Membrane Proteins, MESH: Macrophages, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, RAW 264.7 Cells, chemistry, Gram-Negative Bacterial Infections, MESH: Female, Heme Oxygenase-1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.
Published: 2016
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15. The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Author: Ifrim, Daniela, Quintin, Jessica, Courjol, Flavie, Verschueren, Ineke, van Krieken, J Han, Koentgen, Frank, Fradin, Chantal, Gow, Neil A.R., Joosten, Leo A.B., van Der Meer, Jos, van de Veerdonk, Frank, Netea, Mihai, Radboud University Medical Center [Nijmegen], Lille Inflammation Research International Center - U 995 (LIRIC), 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-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ozgene, University of Aberdeen, This work was supported by European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices 'ALLFUN') to D.C.I., F.C., C.F., M.G.N., and N.A.R.G. M.G.N and J.Q. were supported by a Vici grant of The Netherlands Organization of Scientific Research (to M.G.N.). M.G.N. was supported by an ERC Consolidator Grant (nr. 310372). N.A.R.G. was also supported by the Wellcome Trust (086827, 075470, 097377, & 101873)., European Project: 260338,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ALLFUN(2010), European Project: 310372,EC:FP7:ERC,ERC-2012-StG_20111109,SYSBIOFUN(2013), Jessica, Quintin, Fungi in the setting of inflammation, allergy and autoimmune diseases:Translating basic science into clinical practices - ALLFUN - - EC:FP7:HEALTH2010-12-01 - 2014-05-31 - 260338 - VALID, and The interaction landscape between microbial colonization and functional genome of the host: a systems biology approach in fungal infections - SYSBIOFUN - - EC:FP7:ERC2013-01-01 - 2017-12-31 - 310372 - VALID
Subjects: MESH: Mutation, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Kidney, MESH: Mice, Knockout, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mannans, Mice, MESH: Mannans, Phagocytosis, MESH: Mice, Inbred C57BL, Candida albicans, Animals, Humans, MESH: Animals, Lectins, C-Type, MESH: Phagocytosis, MESH: Mice, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cells, Cultured, Mice, Knockout, MESH: Humans, MESH: Candida albicans, Macrophages, MESH: Host-Pathogen Interactions, Candidiasis, MESH: Macrophages, Research Reports, MESH: Kidney, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Candidiasis, Immunity, Innate, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Disease Models, Animal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, Mutation, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Female, MESH: Disease Models, Animal, MESH: Female, MESH: Lectins, C-Type, MESH: Cells, Cultured
Abstract: International audience; Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.
Published: 2016
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16. Mechanisms Underlying the Delayed Activation of the Cap1 Transcription Factor in Candida albicans following Combinatorial Oxidative and Cationic Stress Important for Phagocytic Potency

Author: Kos, Iaroslava, Patterson, Miranda J, Znaidi, Sadri, Kaloriti, Despoina, da Silva Dantas, Alessandra, Herrero-de-Dios, Carmen M, D'Enfert, Christophe, Brown, Alistair J P, Quinn, Janet, Institute for Cell and Molecular Biosciences, Newcastle University [Newcastle], Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), University of Aberdeen, This work, including the efforts of Alistair J.P. Brown, was funded by Wellcome Trust (097377 and 080088). This work, including the efforts of Janet Quinn, was funded by Wellcome Trust (097377 and 089930). This work, including the efforts of Alistair J.P. Brown, was funded by EC | European Research Council (ERC) (ERC-2009-AdG-249793). This work, including the efforts of Alistair J.P. Brown, was funded by Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F00513X/1 and BB/K017365/1). This work, including the efforts of Janet Quinn, was funded by Biotechnology and Biological Sciences Research Council (BBSRC) (BB/K016393/1). This work, including the efforts of Christophe d’Enfert, was funded by Agence Nationale de la Recherche (ANR) (ANR-14-CE14-0018-01 and ANR-10-LABX-62-IBEID)., ANR-14-CE14-0018,CANDIHUB,Réponse au stress et virulence chez les champignons pathogènes de l'homme : une approche comparative systémique des réseaux de régulation chez les espèces du genre Candida(2014), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 249793,EC:FP7:ERC,ERC-2009-AdG,STRIFE(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], ANR-14-CE14-0018,CANDIHUB,Réponse au stress et virulence chez les champignons pathogènes de l’homme : une approche comparative systémique des réseaux de régulation chez les espèces du genre Candida(2014), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Biologie et Pathogénicité fongiques (BPF), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)
Subjects: protein-kinase, Cell Cycle Proteins, yeast, MESH: Basic-Leucine Zipper Transcription Factors, Microbiology, localization, Fungal Proteins, MESH: Cell Cycle Proteins, Phagocytosis, neutrophils, Osmotic Pressure, Stress, Physiological, Cations, Gene Expression Regulation, Fungal, Candida albicans, yap1, MESH: Stress, Physiological, MESH: Cations, MESH: Phagocytosis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Oxidative Stress, disulfide bond formation, MESH: Candida albicans, MESH: Reactive Oxygen Species, MESH: Osmotic Pressure, QR1-502, signaling pathways, Oxidative Stress, Basic-Leucine Zipper Transcription Factors, MESH: Protein Processing, Post-Translational, responses, MESH: Fungal Proteins, nuclear export, human fungal pathogen, Reactive Oxygen Species, Protein Processing, Post-Translational, MESH: Gene Expression Regulation, Fungal, Research Article
Abstract: Following phagocytosis, microbes are exposed to an array of antimicrobial weapons that include reactive oxygen species (ROS) and cationic fluxes. This is significant as combinations of oxidative and cationic stresses are much more potent than the corresponding single stresses, triggering the synergistic killing of the fungal pathogen Candida albicans by “stress pathway interference.” Previously we demonstrated that combinatorial oxidative plus cationic stress triggers a dramatic increase in intracellular ROS levels compared to oxidative stress alone. Here we show that activation of Cap1, the major regulator of antioxidant gene expression in C. albicans, is significantly delayed in response to combinatorial stress treatments and to high levels of H2O2. Cap1 is normally oxidized in response to H2O2; this masks the nuclear export sequence, resulting in the rapid nuclear accumulation of Cap1 and the induction of Cap1-dependent genes. Here we demonstrate that following exposure of cells to combinatorial stress or to high levels of H2O2, Cap1 becomes trapped in a partially oxidized form, Cap1OX-1. Notably, Cap1-dependent gene expression is not induced when Cap1 is in this partially oxidized form. However, while Cap1OX-1 readily accumulates in the nucleus and binds to target genes following high-H2O2 stress, the nuclear accumulation of Cap1OX-1 following combinatorial H2O2 and NaCl stress is delayed due to a cationic stress-enhanced interaction with the Crm1 nuclear export factor. These findings define novel mechanisms that delay activation of the Cap1 transcription factor, thus preventing the rapid activation of the stress responses vital for the survival of C. albicans within the host., IMPORTANCE Combinatorial stress-mediated synergistic killing represents a new unchartered area in the field of stress signaling. This phenomenon contrasts starkly with “stress cross-protection,” where exposure to one stress protects against subsequent exposure to a different stress. Previously we demonstrated that the pathogen Candida albicans is acutely sensitive to combinations of cationic and oxidative stresses, because the induction of H2O2-responsive genes is blocked in the presence of cationic stress. We reveal that this is due to novel mechanisms that delay activation of the Cap1 AP-1-like transcription factor, the major regulator of the H2O2-induced regulon. Cap1 becomes trapped in a partially oxidized form following simultaneous exposure to oxidative and cationic stresses. In addition, cationic stress promotes the interaction of Cap1 with the Crm1 nuclear export factor, thus inhibiting its nuclear accumulation. These mechanisms probably explain the potency of neutrophils, which employ multiple stresses to kill fungal pathogens.
Published: 2016
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17. A multibiomarker approach on the Atlantic tomcod (Microgadus tomcod) in the St. Lawrence Estuary

Author: Pauline Brousseau, Célie Dupuy, Pierre Nellis, Michel Fournier, Catherine M. Couillard, Jean Laroche, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Pêches et Océans Canada, institut Maurice Lamontagne, and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Quebec, Health, Toxicology and Mutagenesis, MESH: Cell Cycle, 010501 environmental sciences, 01 natural sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunotoxicity, MESH: Animals, Toxicity Tests, Chronic, MESH: Phagocytosis, Principal Component Analysis, 0303 health sciences, geography.geographical_feature_category, Ecology, Gadiformes, Cell Cycle, Age Factors, Quebec, General Medicine, Environmental exposure, Pollution, MESH: Cytochrome P-450 CYP1A1, Liver, Bioaccumulation, %22">Fish , EROD, Female, Estuaries, Immunocompetence, MESH: Environmental Monitoring, MESH: Estuaries, Environmental Monitoring, Chronic exposure, MESH: Environmental Exposure, Zoology, Biology, MESH: Gadiformes, 03 medical and health sciences, Phagocytosis, Cytochrome P-450 CYP1A1, Animals, Environmental Chemistry, Ecotoxicology, 14. Life underwater, 030304 developmental biology, 0105 earth and related environmental sciences, MESH: Age Factors, MESH: Principal Component Analysis, geography, Water Pollution, MESH: Metallothionein, MESH: Biological Markers, MESH: Toxicity Tests, Chronic, Microgadus tomcod, Estuary, Environmental Exposure, biology.organism_classification, MESH: Male, MESH: Immunocompetence, Fish, MESH: Water Pollution, Biometric indexes, Metallothionein, MESH: Female, Biomarkers, MESH: Liver
Abstract: This work was conducted in the environmental immunotoxicology laboratory at Institut Armand Frappier (IAF-INRS). Financial support has been provided by the Canada Research Chair in Environmental Immunotoxicology (Dr. Michel Fournier) and Collège Doctoral International de l'Université européenne de Bretagne. This study was also supported by the INTERREG IV program (DIESE): 50 % of the Ph.D. grant was obtained by the first author, for the development of immune markers in ecotoxicology.; International audience; A multibiomarker approach was developed on juvenile Atlantic tomcod (Microgadus tomcod) to evaluate the pertinence of this approach for low-cost screening assessment of the environmental quality of various coastal sites within estuaries. Several biometric indices and biomarkers (ethoxyresorufin-O-deethylase (EROD) activity, metallothionein concentration, and immune responses) were investigated on immature and maturing tomcods (≤ 31 months) collected in four environmentally contrasted sites in the St. Lawrence Estuary (SLE). Simultaneous examination of various age classes provides the opportunity to detect short-term responses in sensitive young-of-the-year fish (e.g., EROD induction) and longer-time effects associated with chronic exposure and bioaccumulation (e.g., metallothionein induction). Principal component analysis was helpful to discriminate between responses possibly related to contaminant exposure (EROD, metallothionein) and responses that could be affected by upstream-downstream gradient (immune response, biometric indices). Measurement of a battery of biomarkers in young tomcods at several sites along the shore of the SLE is a low-cost screening investigation useful to identify hot spots requiring further investigation with chemical analysis and additional reference sites.
Published: 2012
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18. Autonomous phagosomal degradation and antigen presentation in dendritic cells

Author: Fiorella Kotsias, Eik Hoffmann, Sebastian Amigorena, Ariel Savina, Pierre Bruhns, Geraldine Visentin, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was financed by Institut Curie, Institut National de la Santé et de la Recherche Médicale, Association pour la Recherche sur le Cancer (Grant SFI20101201629), La Ligue Nationale contre le Cancer (Ligue Labellisée 2007–2010 and 2011–2013), the European Research Council (Grant PhagoDC 233062), Agence National de Recherche (MIME, APAT), and the Bettencourt-Schueller Foundation. E.H. was supported by grants from Fondation Recherche Médicale and the AXA Research Fund, F.K. was supported by the European Research Council, and A.S. was supported by the Association pour la Recherche sur le Cancer., ANR-07-MIME-0002,APAT,Presentation croisée et activation des lymphocytes T par les cellules dendritiques(2007), European Project: 233062,EC:FP7:ERC,ERC-2008-AdG,PHAGODC(2009), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Martin, Marie, Microbiologie, immunologie et maladies émergentes - Presentation croisée et activation des lymphocytes T par les cellules dendritiques - - APAT2007 - ANR-07-MIME-0002 - MIME - VALID, Integrative phagosomal biology: antigen presentation and developmental programs in dendritic cells - PHAGODC - - EC:FP7:ERC2009-07-01 - 2014-06-30 - 233062 - VALID, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, Ovalbumin, Antigen presentation, MESH: Microspheres, MESH: Flow Cytometry, Immunoglobulin G, Mice, 03 medical and health sciences, MESH: Phagosomes, 0302 clinical medicine, Immune system, Phagocytosis, Antigen, Phagosomes, Animals, MESH: Animals, MESH: Phagocytosis, MESH: Mice, MESH: Opsonin Proteins, 030304 developmental biology, Phagosome, MESH: Immunoglobulin G, Antigen Presentation, 0303 health sciences, MESH: Ovalbumin, Multidisciplinary, MESH: Dendritic Cells, biology, Antigen processing, Dendritic Cells, Biological Sciences, Opsonin Proteins, Flow Cytometry, Acquired immune system, Microspheres, Cell biology, Antibody opsonization, 030220 oncology & carcinogenesis, MESH: Antigen Presentation, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lysosomes, MESH: Lysosomes
Abstract: This article contains supporting information online at : www.pnas.org/lookup/suppl/doi:10.1073/pnas.1203912109/-/DCSupplemental; International audience; Phagocytosis plays a critical role in both innate and adaptive immunity. Phagosomal fusion with late endosomes and lysosomes enhances proteolysis, causing degradation of the phagocytic content. Increased degradation participates in both innate protection against pathogens and the production of antigenic peptides for presentation to T lymphocytes during adaptive immune responses. Specific ligands present in the phagosomal cargo influence the rate of phagosome fusion with lysosomes, thereby modulating both antigen degradation and presentation. Using a combination of cell sorting techniques and single phagosome flow cytometry-based analysis, we found that opsonization with IgG accelerates antigen degradation within individual IgG-containing phagosomes, but not in other phagosomes present in the same cell and devoid of IgG. Likewise, IgG opsonization enhances antigen presentation to CD4(+) T lymphocytes only when antigen and IgG are present within the same phagosome, whereas cells containing phagosomes with either antigen or IgG alone failed to present antigen efficiently. Therefore, individual phagosomes behave autonomously, in terms of both cargo degradation and antigen presentation to CD4(+) T cells. Phagosomal autonomy could serve as a basis for the intracellular discrimination between self and nonself antigens, resulting in the preferential presentation of peptides derived from opsonized, nonself antigens.
Published: 2012
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19. Differential Recruitment of Activating and Inhibitory FcγRII during Phagocytosis

Author: Patricia Mero, Theodore Pham, Sujata Syam, Pierre Bruhns, James W. Booth, Courtney A.L. McIntosh, Martin, Marie, University of Toronto, Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Grants MOP66961 and MOP84475 from the Canadian Institutes of Health Research., and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, Mutant Chimeric Proteins, MESH: Cricetinae, Antigen-Antibody Complex, MESH: Amino Acid Sequence, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Cricetulus, Cricetinae, Immunology and Allergy, MESH: Animals, MESH: Phagocytosis, Receptor, MESH: Immunoglobulin G, 0303 health sciences, biology, MESH: Mutant Chimeric Proteins, MESH: Antigen-Antibody Complex, Protein Transport, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cricetulus, Cell activation, Protein Binding, Signal Transduction, MESH: Protein Transport, [SDV.IMM] Life Sciences [q-bio]/Immunology, Phagocytosis, Molecular Sequence Data, Immunology, MESH: Receptors, IgG, Inhibitory postsynaptic potential, Cell Line, 03 medical and health sciences, medicine, Extracellular, Animals, Humans, MESH: Protein Binding, Amino Acid Sequence, Fibroblast, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Receptors, IgG, biology.organism_classification, Molecular biology, Protein Structure, Tertiary, MESH: Cell Line, MESH: Extracellular Space, Cell culture, Immunoglobulin G, Extracellular Space, 030215 immunology
Abstract: International audience; Human myeloid cells express both activating and inhibitory receptors of the FcgammaRII family. FcgammaRIIA mediates processes associated with cell activation, including phagocytosis of IgG-opsonized particles, whereas coengagement of the inhibitory FcgammaRIIB downregulates such signaling. We analyzed the relative recruitment of these two receptors during phagocytosis of IgG-coated particles by ts20 Chinese hamster fibroblast cells cotransfected with both receptors carrying distinguishable fluorescent protein tags. We found that FcgammaRIIA is substantially enriched at sites of particle binding relative to its inhibitory counterpart, with a greater than 2-fold increase in the local ratio of activating to inhibitory receptor compared with that for the plasma membrane as a whole. Experiments with chimeric receptors revealed that the preferential enrichment of FcgammaRIIA results from differences between the extracellular domains of the receptors, and indicated that the lesser recruitment of FcgammaRIIB limits its ability to effectively inhibit FcgammaRIIA-mediated phagocytosis. Mutagenesis studies indicated that FcgammaRIIA residues leucine 132 and phenylalanine 160, which lie in IgG-binding regions of FcgammaRIIA and which differ in FcgammaRIIB, both contribute to the local relative enrichment of FcgammaRIIA by increasing its affinity for IgG1 relative to that of FcgammaRIIB. In human monocytes, engagement of approximately equal amounts of FcgammaRIIB was required to substantially inhibit FcgammaRIIA-mediated phagocytosis. These results demonstrate that differences in affinity for IgG between activating and inhibitory FcgammaR can result in substantial local changes in their relative concentrations during phagocytosis, with important functional consequences.
Published: 2010
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20. Development of Monocytes, Macrophages, and Dendritic Cells

Author: Miriam Merad, Steffen Jung, Frederic Geissmann, Michael H. Sieweke, Markus G. Manz, Klaus Ley, Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, University hospital of Zurich [Zurich], Weizmann Institute of Science [Rehovot, Israël], 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), Icahn Medical Institute-Mount Sinai School of Medicine, Department of Gene and Cell Medicine and Institute for Immunology, La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of Zurich, and Geissmann, F
Subjects: MESH: Inflammation, MESH: Myelopoiesis, Transcription, Genetic, Cellular differentiation, MESH: Monocytes, Monocytes, Mice, 0302 clinical medicine, Homeostasis, MESH: Animals, MESH: Phagocytosis, MESH: Myeloid Progenitor Cells, Myelopoiesis, MESH: Cytokines, 0303 health sciences, Multidisciplinary, MESH: Dendritic Cells, Cell biology, medicine.anatomical_structure, MESH: Homeostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, medicine.symptom, 610 Medicine & health, Inflammation, Biology, Article, 03 medical and health sciences, Immune system, Phagocytosis, MESH: Cell Proliferation, medicine, Animals, Humans, Cell Lineage, MESH: Mice, Myeloid Progenitor Cells, Cell Proliferation, 030304 developmental biology, 1000 Multidisciplinary, MESH: Humans, Innate immune system, Cell growth, MESH: Transcription, Genetic, Macrophages, Monocyte, MESH: Macrophages, Dendritic Cells, Dendritic cell, MESH: Cell Lineage, 10032 Clinic for Oncology and Hematology, Immunology, 030215 immunology
Abstract: Development of Myeloid Immune Cells As leukocytes develop to maturity, they proceed through an array of phenotypically distinct intermediates. For T and B lymphocyte populations, the different developmental stages, anatomical locations, and cell signals required for progression are well established. However, until recently, much less has been known about how development proceeds in the myeloid lineage, which includes monocytes, macrophages, and dendritic cells. Geissmann et al. (p. 656 ) review our current understanding of myeloid lineage development and describe the developmental pathways and cues that drive differentiation.
Published: 2010
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21. Effects of ozone, ultraviolet and peracetic acid disinfection of a primary-treated municipal effluent on the Immune system of rainbow trout (Oncorhynchus mykiss)

Author: Christian Blaise, François Gagné, Daniel G. Cyr, Bertrand Bouchard, Michel Fournier, Robert Hausler, P. Cejka, N. Hébert, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Fluvial Ecosystem Research, Environment and Climate Change Canada, Municpal Wastewater Treatment station, Montreal Wastewater Treatment Plant, Station expérimentale des procédés pilotes en environnement, Université du Québec à Montréal = University of Québec in Montréal (UQAM), and This work was supported by the Fonds d'Action Québécois pour le Développement Durable (FAQDD) et le Réseau de Recherche en Écotoxicologie du Saint-Laurent (RRESL).
Subjects: Time Factors, MESH: Quebec, MESH: Peracetic Acid, Physiology, T-Lymphocytes, Health, Toxicology and Mutagenesis, Lymphocyte, Lymphocyte proliferation, Lymphocyte Activation, Toxicology, Biochemistry, chemistry.chemical_compound, MESH: Disinfection, MESH: Water Purification, Peracetic acid, Body Size, MESH: Animals, Food science, MESH: Phagocytosis, Sewage, biology, Quebec, General Medicine, Killer Cells, Natural, Trout, medicine.anatomical_structure, MESH: Oncorhynchus mykiss, Oncorhynchus mykiss, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH: Ozone, MESH: Killer Cells, Natural, Ultraviolet Rays, Phagocytosis, Water Purification, Ozone, Immune system, MESH: Cell Proliferation, MESH: Cities, medicine, Animals, Peracetic Acid, Cities, MESH: Lymphocyte Activation, Effluent, MESH: Sewage, Cell Proliferation, MESH: Body Size, Macrophages, MESH: Time Factors, MESH: Disinfectants, MESH: Macrophages, Cell Biology, biology.organism_classification, Disinfection, MESH: T-Lymphocytes, chemistry, Immunology, MESH: Ultraviolet Rays, Rainbow trout, Disinfectants
Abstract: International audience; Municipal sewage effluents are complex mixtures that are known to compromise the health condition of aquatic organisms. The aim of this study was to evaluate the impacts of various wastewater disinfection processes on the immune system of juvenile rainbow trout (Oncorhynchus mykiss). The trout were exposed to a primary-treated effluent for 28 days before and after one of each of the following treatments: ultraviolet (UV) radiation, ozonation and peracetic acid. Immune function was characterized in leucocytes from the anterior head kidney by the following three parameters: phagocytosis activity, natural cytotoxic cells (NCC) function and lymphocyte (B and T) proliferation assays. The results show that the fish mass to length ratio was significantly decreased for the primary-treated and all three disinfection processes. Exposure to the primary-treated effluent led to a significant increase in macrophage-related phagocytosis; the addition of a disinfection step was effective in removing this effect. Both unstimulated and mitogen-stimulated T lymphocyte proliferation in fish decreased dramatically in fish exposed to the ozonated effluent compared to fish exposed to either the primary-treated effluent or to aquarium water. Stimulation of T lymphocytes proliferation was observed with the peracetic acid treatment group. In conclusion, the disinfection strategy used can modify the immune system in fish at the level of T lymphocyte proliferation but was effective to remove the effects on phagocytosis activity.
Published: 2008
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22. Human Dendritic Cell-Specific Intercellular Adhesion Molecule-Grabbing Nonintegrin (CD209) Is a Receptor forYersinia pestisThat Promotes Phagocytosis by Dendritic Cells

Author: Silvia Bulgheresi, Ramaswamy Kalyanasundaram, Tie Chen, Mikael Skurnik, B. Joseph Hinnebusch, John D. Klena, Shusheng Zhang, Olivier Schwartz, Pei Zhang, Johnny J. He, Department of Biomedical Sciences, College of Medicine, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Faculty of Life Sciences, University of Vienna [Vienna], Department of Microbiology and Immunology, Indiana University School of Medicine, Indiana University System-Indiana University System, School of Biological Sciences, University of Canterbury [Christchurch], Laboratory of Zoonotic Pathogens, National Institutes of Health, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lipopolysaccharides, MESH: Macrophages, Alveolar, Yersinia pestis, Phagocytosis, Immunology, MESH: Yersinia pestis, Receptors, Cell Surface, Models, Biological, Microbiology, Cell Line, 03 medical and health sciences, Macrophages, Alveolar, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Lectins, C-Type, MESH: Phagocytosis, Receptor, Cells, Cultured, MESH: Receptors, Cell Surface, 030304 developmental biology, 0303 health sciences, MESH: Humans, Cellular Microbiology: Pathogen-Host Cell Molecular Interactions, MESH: Dendritic Cells, biology, 030306 microbiology, Cell adhesion molecule, MESH: Models, Biological, Dendritic Cells, Dendritic cell, biology.organism_classification, Intercellular adhesion molecule, Enterobacteriaceae, MESH: Cell Line, 3. Good health, Infectious Diseases, Cell culture, MESH: Cell Adhesion Molecules, Parasitology, MESH: Lipopolysaccharides, Cell Adhesion Molecules, MESH: Lectins, C-Type, MESH: Cells, Cultured
Abstract: Yersinia pestisis the etiologic agent of bubonic and pneumonic plagues. It is speculated thatY. pestishijacks antigen-presenting cells (APCs), such as dendritic cells (DCs) and alveolar macrophages, in order to be delivered to lymph nodes. However, how APCs initially capture the bacterium remains uncharacterized. It is well known that HIV-1 uses human DC-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) (CD209) receptor, expressed by APCs, to be captured and delivered to target cell, such as CD4+lymphocytes. Several gram-negative bacteria utilize their core lipopolysaccharides (LPS) as ligands to interact with the human DC-SIGN. Therefore, it is possible thatY. pestis, whose core LPS is naturally exposed, might exploit DC-SIGN to invade APCs. We demonstrate in this study thatY. pestisdirectly interacts with DC-SIGN and invades both DCs and alveolar macrophages. In contrast, when engineered to cover the core LPS,Y. pestisloses its ability to invade DCs, alveolar macrophages, and DC-SIGN-expressing transfectants. The interaction betweenY. pestisand human DCs can be reduced by a combination treatment with anti-CD209 and anti-CD207 antibodies. This study shows that human DC-SIGN is a receptor forY. pestisthat promotes phagocytosis by DCs in vitro.
Published: 2008
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23. Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae

Author: Marcello Salvatore Lenucci, Shih-Chin Cheng, Noemi Tocci, Vasilis Oikonomou, Tobias Weil, Lisa Rizzetto, Silvia Moretti, Daniela C. Ifrim, Manuel A. S. Santos, Mihai G. Netea, Bastiaan A. Blok, Duccio Cavalieri, Giorgia Renga, Luigina Romani, Jessica Quintin, Carlotta De Filippo, Rizzetto, Lisa, Ifrim, Daniela C, Moretti, Silvia, Tocci, Noemi, Cheng, Shih Chin, Quintin, Jessica, Renga, Giorgia, Oikonomou, Vasili, De Filippo, Carlotta, Weil, Tobia, Blok, Bastiaan A, Lenucci, Marcello Salvatore, Santos, Manuel A. S, Romani, Luigina, Netea, Mihai G, Cavalieri, Duccio, Centro Ricerca e Innovazione - Research and Innovation Centre [FEM - Italie], Fondazione Edmund Mach - Edmund Mach Foundation [Italie] (FEM), Radboud University Medical Center [Nijmegen], Università degli Studi di Perugia (UNIPG), Università del Salento [Lecce], Universidade de Aveiro, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Istituto di Biometeorologia [Firenze] (IBIMET), Consiglio Nazionale delle Ricerche (CNR), This work was supported from the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant Agreement HEALTH-2010-242220 ('SYBARIS', to D. C), by a Vici grant from the Netherlands Organization for Scientific Research (to J. Q., S.-C. C., and M. G. N.), by ERC Consolidator Grant 310372 (to M. G. N.), by European Union's Seventh Framework Programme (FP7/2007–2013) under Grant Agreement HEALTH-2010-260338 ('ALLFUN', to D. C. I. and M. G. N.), and by the MetafoodbookLabs grant from Provincia Autonoma di Trento and UNIFARM (to D. C., L. R., N. T., and T. W.). The authors declare that they have no conflicts of interest with the contents of this article., European Project: 242220,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,SYBARIS(2009), European Project: 310372,EC:FP7:ERC,ERC-2012-StG_20111109,SYSBIOFUN(2013), European Project: 260338,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ALLFUN(2010), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli Studi di Firenze = University of Florence (UniFI), and National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Chitin, host-pathogen interaction, MESH: Monocytes, Inbred C57BL, Monocyte, Saccharomyces, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Biochemistry, MESH: Chitin, Monocytes, Mice, 0302 clinical medicine, Cell Wall, Innate, MESH: Animals, Fungal chitin, Internalization, MESH: Phagocytosis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, media_common, Cell wall, MESH: Saccharomyces cerevisiae, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Settore BIO/19 - MICROBIOLOGIA GENERALE, Human, Phagosome acidification, Phagocytosis, Host–pathogen interaction, media_common.quotation_subject, Immunology, Trained immunity, Saccharomyces cerevisiae, Biology, Microbiology, 03 medical and health sciences, Immune system, MESH: Cell Wall, Immunity, MESH: Mice, Inbred C57BL, cell wall, cellular immune response, fungi, phagocytosis, Animals, Humans, Interleukin-6, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Immunity, Innate, Molecular Biology, Cell Biology, Phagocytosi, Host-pathogen interaction, MESH: Humans, Host (biology), Animal, Fungi, Cellular immune response, biology.organism_classification, MESH: Interleukin-6, 030104 developmental biology, MESH: Tumor Necrosis Factor-alpha, 030215 immunology
Abstract: This research was originally published in the Journal of Biological Chemistry. Lisa Rizzetto, Daniela C. Ifrim, Silvia Moretti, Noemi Tocci, Shih-Chin Cheng, Jessica Quintin, Giorgia Renga, Vasilis Oikonomou, Carlotta De Filippo, Tobias Weil, Bastiaan A. Blok, Marcello S. Lenucci, Manuel A. S. Santos, Luigina Romani, Mihai G. Netea, and Duccio Cavalieri. Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae. J. Biol. Chem. 2016 291: 7961-7972 © the American Society for Biochemistry and Molecular Biology; International audience; The immune system is essential to maintain the mutualistic homeostatic interaction between the host and its micro- and mycobiota. Living as a commensal,Saccharomyces cerevisiaecould potentially shape the immune response in a significant way. We observed thatS. cerevisiaecells induce trained immunity in monocytes in a strain-dependent manner through enhanced TNFα and IL-6 production upon secondary stimulation with TLR ligands, as well as bacterial and fungal commensals. Differential chitin content accounts for the differences in training properties observed among strains, driving induction of trained immunity by increasing cytokine production and direct antimicrobial activity bothin vitroandin vivo These chitin-induced protective properties are intimately associated with its internalization, identifying a critical role of phagosome acidification to facilitate microbial digestion. This study reveals how commensal and passenger microorganisms could be important in promoting health and preventing mucosal diseases by modulating host defense toward pathogens and thus influencing the host microbiota-immune system interactions.
Published: 2016
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24. HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup

Author: Hocine Yezid, Solène Debaisieux, Antoine Gross, Daniel Henaff, Simon Lachambre, Clément Mettling, Sébastien Besteiro, Christophe Chopard, Jean-Michel Mesnard, Bruno Beaumelle, Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Gross, Antoine, Institut de Recherche en Infectiologie de Montpellier (IRIM), Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Phosphatidylinositol 4,5-Diphosphate, MESH: Signal Transduction, Phagocytic cup, Neutrophils, General Physics and Astronomy, MESH: Neutrophils, MESH: Monocytes, Monocytes, MESH: Recombinant Proteins, MESH: HIV-1, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pseudopodia, cdc42 GTP-Binding Protein, MESH: Phagocytosis, ComputingMilieux_MISCELLANEOUS, MESH: Receptors, Cell Surface, 0303 health sciences, Multidisciplinary, MESH: Bystander Effect, MESH: Toxoplasma, MESH: Gene Expression Regulation, Recombinant Proteins, MESH: Phosphatidylinositol 4,5-Diphosphate, 3. Good health, Cell biology, Protein Transport, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, tat Gene Products, Human Immunodeficiency Virus, Signal transduction, Toxoplasma, Mannose Receptor, Signal Transduction, MESH: Protein Transport, MESH: Mycobacterium avium, Phagocytosis, Primary Cell Culture, Receptors, Cell Surface, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Receptors, IgG, Biology, General Biochemistry, Genetics and Molecular Biology, MESH: Primary Cell Culture, 03 medical and health sciences, MESH: Mannose-Binding Lectins, Extracellular, Humans, Lectins, C-Type, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Phosphatidylinositol, Opsonin, 030304 developmental biology, MESH: tat Gene Products, Human Immunodeficiency Virus, MESH: cdc42 GTP-Binding Protein, MESH: Humans, Macrophages, Receptors, IgG, MESH: Host-Pathogen Interactions, MESH: Macrophages, Bystander Effect, General Chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cytosol, Mannose-Binding Lectins, Gene Expression Regulation, chemistry, Cell culture, MESH: Pseudopodia, HIV-1, MESH: Lectins, C-Type, 030217 neurology & neurosurgery, Mycobacterium avium
Abstract: International audience; Most macrophages remain uninfected in HIV-1-infected patients. Nevertheless, the phagocytic capacity of phagocytes from these patients is impaired, favouring the multiplication of opportunistic pathogens. The basis for this phagocytic defect is not known. HIV-1 Tat protein is efficiently secreted by infected cells. Secreted Tat can enter uninfected cells and reach their cytosol. Here we found that extracellular Tat, at the subnanomolar concentration present in the sera of HIV-1-infected patients, inhibits the phagocytosis of Mycobacterium avium or opsonized Toxoplasma gondii by human primary macrophages. This inhibition results from a defect in mannose- and Fcγ-receptor-mediated phagocytosis, respectively. Inhibition relies on the interaction of Tat with phosphatidylinositol (4,5)bisphosphate that interferes with the recruitment of Cdc42 to the phagocytic cup, thereby preventing Cdc42 activation and pseudopod elongation. Tat also inhibits FcγR-mediated phagocytosis in neutrophils and monocytes. This study provides a molecular basis for the phagocytic defects observed in uninfected phagocytes following HIV-1 infection.
Published: 2015
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25. Evidence for a subventricular zone neural stem cell phagocytic activity stimulated by the vitamin K-dependent factor protein S

Author: Aurore Gely-Pernot, Aurélie Ginisty, Valérie Coronas, Patricia Arnault, Loubna Abaamrane, Franck Morel, Omar Benzakour, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, and Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH: Neural Stem Cells, animal diseases, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Subventricular zone, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Protein S, Mice, SOX2, Neural Stem Cells, Phagocytosis, Lateral Ventricles, Proto-Oncogene Proteins, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, MESH: Animals, Efferocytosis, MESH: Phagocytosis, MESH: Mice, Tissue homeostasis, Cells, Cultured, MESH: Lateral Ventricles, c-Mer Tyrosine Kinase, Receptor Protein-Tyrosine Kinases, Cell Biology, Nestin, MERTK, Antigens, Differentiation, Neural stem cell, Cell biology, MESH: Protein S, MESH: Proto-Oncogene Proteins, medicine.anatomical_structure, Neuropoiesis, nervous system, MESH: Antigens, Differentiation, Molecular Medicine, MESH: Receptor Protein-Tyrosine Kinases, Developmental Biology, Signal Transduction, MESH: Cells, Cultured
Abstract: Neural stem cells, whose major reservoir in the adult mammalian brain is the subventricular zone (SVZ), ensure neuropoiesis, a process during which many generated cells die. Removal of dead cells and debris by phagocytes is necessary for tissue homeostasis. Using confocal and electron microscopy, we demonstrate that cultured SVZ cells phagocytose both 1 and 2 µm latex beads and apoptotic cell-derived fragments. We determine by flow cytometry that phagocytic cells represent more than 10% of SVZ cultured cells. Phenotyping of SVZ cells using nestin, GFAP, Sox2, or LeX/SSEA and quantification of aldehyde dehydrogenase (ALDH) activity, reveals that cells with neural stem-cell features phagocytose and represent more than 30% of SVZ phagocytic cells. In vivo, nestin-, Sox2-, and ALDH-expressing neural stem-like cells engulfed latex beads or apoptotic cell-derived fragments that were injected into mice lateral brain ventricles. We show also that SVZ cell phagocytic activity is an active process, which depends both on cytoskeleton dynamic and on recognition of phosphatidylserine eat-me signal, and is stimulated by the vitamin K-dependent factor protein S (ProS). ProS neutralizing antibodies inhibit SVZ cell phagocytic activity and exposure of SVZ cells to apoptotic cell-derived fragments induces a transient Mer tyrosine kinase receptor (MerTK) phosphorylation. Conversely, MerTK blocking antibodies impair both basal and ProS-stimulated SVZ cell phagocytic activity. By revealing that neural stem-like cells act within the SVZ neurogenic niche as phagocytes and that the ProS/MerTK path represents an endogenous regulatory mechanism for SVZ cell phagocytic activity, the present report opens-up new perspectives for both stem cell biology and brain physiopathology. Stem Cells 2015;33:515–525
Published: 2015
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26. Cellular bioterrorism: how Brucella corrupts macrophage physiology to promote invasion and proliferation

Author: Maria-Pilar, Jimenez de Bagues, Jimenez de Bagues, Maria-Pilar, Sherri, Dudal, Jacques, Dornand, Antoine, Gross, Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Infectiologie de Montpellier (IRIM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lipopolysaccharides, Immunology, Virulence, MESH: Cyclic AMP-Dependent Protein Kinases, Brucella, MESH: Virulence, Phagolysosome, Brucellosis, Microbiology, Mice, 03 medical and health sciences, 0302 clinical medicine, Phagocytosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Brucellosis, Cyclic AMP, Animals, Humans, Immunology and Allergy, Macrophage, MESH: Animals, Secretion, MESH: Phagocytosis, MESH: Mice, Lipid raft, MESH: Cyclic AMP, 030304 developmental biology, 0303 health sciences, MESH: Humans, biology, MESH: Brucella, Cell growth, Macrophages, Intracellular parasite, MESH: Macrophages, biology.organism_classification, Cyclic AMP-Dependent Protein Kinases, MESH: Mitogen-Activated Protein Kinases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mitogen-Activated Protein Kinases, MESH: Lipopolysaccharides, Cell Division, 030215 immunology
Abstract: Brucellosis is a worldwide human zoonosis caused by intracellular bacteria of the genus Brucella. Virulence factors play an important role in allowing Brucella infection and proliferation within macrophages. Brucella enters macrophages through lipid raft microdomains, avoids phagolysosome fusion, and inhibits TNF-alpha secretion and apoptosis. Furthermore, Brucella can perturb bactericidal activity in macrophages by influencing the host cell response to its advantage through its LPS or by activating the cAMP/PKA pathway. To date, small steps have been taken in defining and understanding the virulence factors of Brucella used in macrophage subversion, but further investigation is required to fully explain virulence and persistence.
Published: 2005
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27. Subversion and Utilization of the Host Cell Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway by Brucella During Macrophage Infection

Author: Pierre Casellas, Jean-Pierre Liautard, Jacques Dornand, Monsif Bouaboula, Antoine Gross, Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département immunologie-oncologie, and Sanofi-Synthélabo
Subjects: MESH: Signal Transduction, Brucella suis, MESH: Sulfonamides, MESH: Virulence, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Piperidines, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cyclic AMP, Tumor Cells, Cultured, Immunology and Allergy, Enzyme Inhibitors, Phosphorylation, Cyclic AMP Response Element-Binding Protein, MESH: Phagocytosis, Receptor, MESH: Cyclic AMP, MESH: Brucella suis, Sulfonamides, Virulence, MESH: Macrophage Activation, MESH: Piperidines, MESH: Enzyme Inhibitors, Rimonabant, Signal transduction, MESH: Dose-Response Relationship, Immunologic, Signal Transduction, MESH: Cyclic AMP Response Element-Binding Protein, MESH: Enzyme Activation, Cell signaling, Immunology, Dose-Response Relationship, Immunologic, Enzyme Activators, MESH: Cyclic AMP-Dependent Protein Kinases, Brucella, Biology, CREB, Microbiology, Phagocytosis, MESH: Isoquinolines, Humans, MESH: Enzyme Activators, MESH: Tumor Cells, Cultured, Protein kinase A, Transcription factor, MESH: Humans, MESH: Phosphorylation, Macrophages, MESH: Macrophages, Macrophage Activation, Isoquinolines, biology.organism_classification, Cyclic AMP-Dependent Protein Kinases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Enzyme Activation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biology.protein, Pyrazoles, MESH: Pyrazoles
Abstract: Brucella spp. are intramacrophage pathogens that induce chronic infections in a wide range of mammals, including domestic animals and humans. Therefore, the macrophage response to infection has important consequences for both the survival of phagocytosed bacteria and the further development of host immunity. However, very little is known about the macrophage cell signaling pathways initiated upon infection and the virulence strategy that Brucella use to counteract these responses and secure their survival. In a previous study, we have shown that macrophages activated by SR141716A, a ligand of the cannabinoid receptor CB1, acquired the capacity to control Brucella and observed that the CB1 receptor-triggering engages the microbicidal activity of phagocytes. To analyze the perturbation of cell signaling pathway during macrophage infection by Brucella, we hypothesized that SR141716A provides cell signaling that interferes with the bacterial message leading to inhibition of macrophage functions. As CB1 receptor belongs to the family of G protein-linked receptors, we explored the cAMP signaling pathway. In this study, we show that the CB1 ligand inhibited the bacteria-induced cell signaling. Taking advantage of this result, we then demonstrated that Brucella infection elicited a rapid activation of the cAMP/protein kinase A pathway. This activation resulted in a prolonged phosphorylation of the transcription factor CREB. We finally demonstrate that the activation of the cAMP/protein kinase A pathway is crucial for the survival and establishment of Brucella within macrophages. For the first time in phagocytes, we thus characterized a primordial virulence strategy of Brucella involving the host signaling pathway, a novel point of immune intervention of this virulent pathogen.
Published: 2003
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28. Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2-Mediated Tissue Repair during Bacterial Infection

Author: Grégory Jouvion, Camille Blériot, Olivier Disson, Théo Dupuis, Marc Lecuit, Gérard Eberl, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), This work was financed by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Institut Carnot, Fondation pour la Recherche Médicale, Ville de Paris, Fondation BNP Paribas, LabEx IBEID, the European Research Council, and Listress EU program., We thank the members of the Biology of Infection Unit, and in particular Y.H. Tsai. We thank G. Milon and S. Berrè for helpful discussions and critical reading of the manuscript. We thank H. Bierne for her contribution in the initial phase of the project and P. Cossart for providing the Lm Δhly mutant. We thank T. Walzer at ENS Lyon for Ccr2−/− mice, Ph. Bousso and F. Montalvao for MaFIA-GFP mice and helpful discussions, M. Leite de Moraes for Il4−/− mice, B. Ryffel for Il1rl1−/− mice, V. Dixit for Rip3−/− mice, T. Taniguchi for Irf3−/− mice, R. Menard for Flk1-gfp mice, and M. Albert and N. Yatim for Casp1−/− and Ifnar−/− mice and helpful discussions. We thank S. Novault of the PFC at Institut Pasteur and N. Sérafini for their help in the FACS experiments., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 116472,FCT::,ERA-PTG/2010,ERA-PTG/0003/2010(2011), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: MESH: Inflammation, Necrosis, Cellular differentiation, [SDV]Life Sciences [q-bio], Complement Pathway, Alternative, MESH: Listeria monocytogenes, MESH: Monocytes, Monocytes, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Macrophage, Immunology and Allergy, Homeostasis, Listeriosis, MESH: Animals, MESH: Phagocytosis, Cells, Cultured, 0303 health sciences, Kupffer cell, Cell Differentiation, medicine.anatomical_structure, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, MESH: Homeostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Interleukins, MESH: Interleukin-33, Kupffer Cells, Necroptosis, Immunology, Inflammation, Mice, Inbred Strains, Biology, MESH: Mice, Inbred Strains, 03 medical and health sciences, Immune system, Phagocytosis, medicine, Animals, MESH: Mice, 030304 developmental biology, MESH: Necrosis, Wound Healing, Monocyte, Interleukins, MESH: Interleukin-4, Interleukin-33, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Wound Healing, MESH: Kupffer Cells, MESH: Listeriosis, Interleukin-4, MESH: Complement Pathway, Alternative, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, MESH: Liver
Abstract: International audience; Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.
Published: 2015
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29. Complement Receptor 3 (CD11b/CD18) Mediates Type I and Type II Phagocytosis During Nonopsonic and Opsonic Phagocytosis, Respectively

Author: Isabelle Maridonneau-Parini, Véronique Le Cabec, Christine Bordier, André Moisand, Sébastien Carréno, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH: Cricetinae, MESH: Recombinant Proteins, chemistry.chemical_compound, 0302 clinical medicine, Cricetinae, Immunology and Allergy, MESH: Animals, MESH: Phagocytosis, Receptor, Internalization, MESH: Opsonin Proteins, media_common, MESH: Immunoglobulin G, MESH: Macrophage-1 Antigen, 0303 health sciences, Chinese hamster ovary cell, hemic and immune systems, Opsonin Proteins, Recombinant Proteins, src-Family Kinases, Mycobacterium kansasii, MESH: Mycobacterium kansasii, Signal transduction, Signal Transduction, MESH: Zymosan, media_common.quotation_subject, Phagocytosis, MESH: Complement System Proteins, Immunology, Macrophage-1 Antigen, chemical and pharmacologic phenomena, CHO Cells, MESH: Microscopy, Electron, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Transfection, Microbiology, 03 medical and health sciences, MESH: CHO Cells, Animals, Humans, Kinase activity, Opsonin, 030304 developmental biology, MESH: Humans, MESH: Transfection, Zymosan, Complement System Proteins, Microscopy, Electron, MESH: src-Family Kinases, chemistry, Immunoglobulin G, 030217 neurology & neurosurgery
Abstract: Two types of opsonic phagocytosis have been defined depending on the receptor engaged: FcγRs mediate type I phagocytosis of IgG-coated particles; complement receptor 3 (CR3) mediates type II phagocytosis of complement-coated particles. In addition to opsonic phagocytosis, CR3 also mediates nonopsonic phagocytosis of zymosan (Z) and Mycobacterium kansasii through engagement of distinct sites. Using Chinese hamster ovary cells stably expressing human CR3, we studied CR3-mediated ingestion of nonopsonized particles, Z or M. kansasii, compared with opsonized zymosan (OZ). We show that 1) while OZ sinks into cells, Z is engulfed by pseudopodia as visualized by electron microscopy; 2) in contrast to OZ, nonopsonic phagocytosis of Z and M. kansasii depends on Rac and Cdc42 but not on Rho activity; and 3) CR3-mediated phagocytosis of Z depends on the kinase activity of the Src family tyrosine kinase Hck, while OZ internalization does not. Therefore, CR3 mediates type I phagocytosis under nonopsonic conditions and type II under opsonic conditions. This is the first evidence that a single receptor can mediate both types of phagocytosis depending on the ligand used.
Published: 2002
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30. Acute exposure to silica nanoparticles enhances mortality and increases lung permeability in a mouse model of Pseudomonas aeruginosa pneumonia

Author: Delaval, Mathilde, Boland, Sonja, Solhonne, Brigitte, Nicola, Marie-Anne, Mornet, Stéphane, Baeza-Squiban, Armelle, Sallenave, Jean-Michel, Garcia-Verdugo, Ignacio, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Défense innée et inflammation, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Dynamique (Plate-Forme) (PFID), Institut Pasteur [Paris], Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, This work was supported by the INSERM, Université Paris 7 Diderot and ANSES EST 2010/2/79 project, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and BMC, BMC
Subjects: Male, Alveolar macrophages, MESH: Macrophages, Alveolar, MESH: Pulmonary Alveoli, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Toxicology, MESH: Animals, MESH: Phagocytosis, Lung, Inhalation Exposure, Alveolar permeability, MESH: Cytokines, MESH: Pseudomonas Infections, respiratory system, MESH: Immunoglobulin M, [SDV] Life Sciences [q-bio], MESH: Survival Analysis, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, Cytokines, MESH: Inhalation Exposure, SiO2, Infection, Bronchoalveolar Lavage Fluid, MESH: Pneumonia, Bacterial, Surface Properties, Capillary Permeability, Phagocytosis, MESH: Mice, Inbred C57BL, Selenium Oxides, Pseudomonas, Macrophages, Alveolar, Pneumonia, Bacterial, Animals, Pseudomonas Infections, MESH: Particle Size, Particle Size, Inflammation, MESH: Surface Properties, MESH: Bronchoalveolar Lavage Fluid, Research, MESH: Capillary Permeability, MESH: Selenium Oxides, Survival Analysis, MESH: Male, Mice, Inbred C57BL, Pulmonary Alveoli, Immunoglobulin M, Nanoparticles, MESH: Nanoparticles
Abstract: Background The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants. The consequences of nanoparticle exposure in the context of lung infection have not been studied in detail. Previous reports have shown that sequential lung exposure to nanoparticles and bacteria may impair bacterial clearance resulting in increased lung bacterial loads, associated with a reduction in the phagocytic capacity of alveolar macrophages. Results Here we have studied the consequences of SiO2 nanoparticle exposure on Pseudomonas aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury in a mouse model of acute pneumonia. We observed that pre-exposure to SiO2 nanoparticles increased mice susceptibility to lethal pneumonia but did not modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain. Furthermore, internalisation of SiO2 nanoparticles by primary alveolar macrophages did not reduce the capacity of the cells to clear Pseudomonas aeruginosa. In our murine model, SiO2 nanoparticle pre-exposure preferentially enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by the measurement of alveolar albumin and IgM concentrations) rather than contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by leukocyte recruitment and cytokine concentration in the alveolar compartment). Conclusions We show that pre-exposure to SiO2 nanoparticles increases mice susceptibility to lethal pneumonia but independently of macrophage phagocytic function. The deleterious effects of SiO2 nanoparticle exposure during Pseudomonas aeruginosa-induced pneumonia are related to alterations of the alveolar-capillary barrier rather than to modulation of the inflammatory responses. Electronic supplementary material The online version of this article (doi:10.1186/s12989-014-0078-9) contains supplementary material, which is available to authorized users.
Published: 2014
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31. Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata

Author: Daniela C, Ifrim, Judith M, Bain, Delyth M, Reid, Marije, Oosting, Ineke, Verschueren, Neil A R, Gow, J Han, van Krieken, Gordon D, Brown, Bart-Jan, Kullberg, Leo A B, Joosten, Jos W M, van der Meer, Frank, Koentgen, Lars P, Erwig, Jessica, Quintin, Mihai G, Netea, Radboud University Medical Center [Nijmegen], University of Aberdeen, and Ozgene
Subjects: Neutrophils, [SDV]Life Sciences [q-bio], Candida glabrata, MESH: Neutrophils, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mice, Phagocytosis, MESH: Mice, Inbred C57BL, Candida albicans, Animals, Lectins, C-Type, MESH: Animals, MESH: Phagocytosis, MESH: Candida glabrata, MESH: Mice, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Host Response and Inflammation, MESH: Cytokines, Macrophages, MESH: Candida albicans, Candidiasis, MESH: Reactive Oxygen Species, MESH: Macrophages, Th1 Cells, MESH: Candidiasis, Mice, Inbred C57BL, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Th1 Cells, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Reactive Oxygen Species, MESH: Female, MESH: Lectins, C-Type
Abstract: International audience; Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here, we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2(-/-) mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate yet significant decrease in phagocytosis of the fungus by the Dectin-2(-/-) macrophages and neutrophils. Neutrophils of Dectin-2(-/-) mice also displayed lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights into the host defense mechanisms against this important fungal pathogen.
Published: 2014
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32. The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging

Author: Jacques Deguine, Nico van Rooijen, Fabricio Montalvao, Philippe Bousso, Zacarias Garcia, Susanna Celli, Béatrice Breart, Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), VU University Medical Center [Amsterdam], We thank F. Lemaître for help in the generating cell lines. This work was supported by Institut Pasteur, INSERM, the Fondation pour la Recherche Médicale, and an European Research Council starting grant (LymphocyteContacts)., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis
Subjects: MESH: Antigens, CD20, MESH: Antibodies, Monoclonal, Mice, 0302 clinical medicine, MESH: Animals, MESH: Phagocytosis, B-Lymphocytes, 0303 health sciences, Brief Report, Optical Imaging, Antibodies, Monoclonal, General Medicine, MESH: Fluorescent Dyes, Burkitt Lymphoma, Liver regeneration, 3. Good health, medicine.anatomical_structure, Lymphatic system, Liver, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Liver Regeneration, Antibody, Lymphoma, B-Cell, Kupffer Cells, Lymphoid Tissue, MESH: Mice, Transgenic, Phagocytosis, Mice, Transgenic, Biology, Lymphocyte Depletion, 03 medical and health sciences, Antigen, In vivo, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, medicine, Animals, MESH: Mice, B cell, Fluorescent Dyes, 030304 developmental biology, MESH: Lymphoma, B-Cell, MESH: Lymphocyte Depletion, MESH: Optical Imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Antigens, CD20, medicine.disease, Liver Regeneration, Lymphoma, Mice, Inbred C57BL, MESH: Burkitt Lymphoma, Disease Models, Animal, MESH: Kupffer Cells, Liposomes, Immunology, MESH: Lymphoid Tissue, Cancer research, biology.protein, MESH: Liposomes, Clodronic Acid, MESH: Disease Models, Animal, MESH: Liver, MESH: Clodronic Acid
Abstract: International audience; Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs.
Published: 2013
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33. L14. Immunomodulatory properties of apoptotic cells

Author: Philippe Saas, Sylvain Perruche, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Saas, Philippe, 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), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), 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]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), and Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Inflammation, MESH: Signal Transduction, Cell Transplantation, Neutrophils, medicine.medical_treatment, Apoptosis, MESH: T-Lymphocyte Subsets, Pharmacology, MESH: Neutrophils, T-Lymphocytes, Regulatory, MESH : Neutrophils, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, T-Lymphocyte Subsets, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Antigen-Presenting Cells, MESH: Desensitization, Immunologic, MESH: Phagocytosis, ComputingMilieux_MISCELLANEOUS, Desensitization (medicine), MESH : Macrophages, 0303 health sciences, Phagocytes, tolerance, MESH: Dendritic Cells, MESH: Antigen-Presenting Cells, MESH : Immune Tolerance, General Medicine, MESH: Chemokines, MESH: Cell Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Chemokines, Inflammation Mediators, medicine.symptom, Signal Transduction, TGF-β, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Inflammation Mediators, MESH: Immunomodulation, Antigen-Presenting Cells, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Inflammation, Immunomodulation, MESH : Inflammation Mediators, 03 medical and health sciences, MESH: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Cell transplantation, Text mining, Phagocytosis, MESH : Phagocytosis, Immune Tolerance, medicine, Animals, Humans, MESH : Chemokines, 030304 developmental biology, MESH : Immunomodulation, MESH : Signal Transduction, MESH: Humans, MESH : Inflammation, business.industry, Macrophages, MESH: T-Lymphocytes, Regulatory, MESH: Apoptosis, MESH : Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, MESH : Humans, MESH: Macrophages, Dendritic Cells, MESH : T-Lymphocyte Subsets, MESH : Cell Transplantation, Desensitization, Immunologic, inflammation, MESH : Dendritic Cells, MESH : Desensitization, Immunologic, MESH : Animals, business, MESH : Apoptosis, 030215 immunology
Abstract: International audience
Published: 2013
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34. From amoeba to macrophages: exploring the molecular mechanisms of Legionella pneumophila infection in both hosts

Author: Pedro, Escoll, Monica, Rolando, Laura, Gomez-Valero, Carmen, Buchrieser, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work received financial support from the Institut Pasteur, the Centre National de la Recherche (CNRS), the Institut Carnot-Pasteur MI, the Fondation pour la Recherche Médicale (FRM) grant N° DEQ20120323697, the French region Ile-de-France (DIM Malinf) and the grant n°ANR-10-LABX-62-IBEID. M. Rolando is holder of a Roux contract financed by the Institut Pasteur., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Humans, MESH: Legionella pneumophila/pathogenicity, Macrophages, MESH: Macrophages/immunology, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, biochemical phenomena, metabolism, and nutrition, Endocytosis, Legionella pneumophila, respiratory tract diseases, MESH: Vacuoles/microbiology, MESH: Legionnaires' Disease/immunology, Phagocytosis, Vacuoles, parasitic diseases, MESH: Amoeba/microbiology, MESH: Endocytosis, MESH: Macrophages/microbiology, Humans, bacteria, Legionnaires' Disease, Amoeba, MESH: Phagocytosis
Abstract: International audience; Legionella pneumophila is a Gram-negative bacterium and the causative agent of Legionnaires' disease. It replicates within amoeba and infects accidentally human macrophages. Several similarities are seen in the L. pneumophila-infection cycle in both hosts, suggesting that the tools necessary for macrophage infection may have evolved during co-evolution of L. pneumophila and amoeba. The establishment of the Legionella-containing vacuole (LCV) within the host cytoplasm requires the remodeling of the LCV surface and the hijacking of vesicles and organelles. Then L. pneumophila replicates in a safe intracellular niche in amoeba and macrophages. In this review we will summarize the existing knowledge of the L. pneumophila infection cycle in both hosts at the molecular level and compare the factors involved within amoeba and macrophages. This knowledge will be discussed in the light of recent findings from the Acanthamoeba castellanii genome analyses suggesting the existence of a primitive immune-like system in amoeba.
Published: 2013
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35. Primary Effusion Lymphoma Cell Death Induced by Bortezomib and AG 490 Activates Dendritic Cells through CD91

Author: Luigi Frati, Roberta Gonnella, Livia Di Renzo, Pankaj Trivedi, Valeria Conte, Alberto Faggioni, Lavinia Vittoria Lotti, Roberta Santarelli, Mara Cirone, Department of Experimental Medicine [Roma], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and This work was partially supported by grants from Ministero dell'Istruzione, dell'Universita ' e della Ricerca, Associazione Italiana per la ricerca sul Cancro, progetto strategico ISS 9ACF/1 of Ministero della salute, and Pasteur Cenci-Bolognetti foundation.
Subjects: Anatomy and Physiology, medicine.medical_treatment, lcsh:Medicine, Apoptosis, immunogenicity, Bortezomib, calreticulin, 0302 clinical medicine, Immune Physiology, hemic and lymphatic diseases, Molecular Cell Biology, MESH: Lymphoma, Primary Effusion, Signaling in Cellular Processes, Cytotoxic T cell, lcsh:Science, MESH: Phagocytosis, MESH: HSP70 Heat-Shock Proteins, 0303 health sciences, Multidisciplinary, MESH: Dendritic Cells, MESH: Kinetics, Chemistry, Tyrphostins, Boronic Acids, 3. Good health, Cell biology, Protein Transport, dying tumor cell, Oncology, Pyrazines, MESH: Pyrazines, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Boronic Acids, Primary effusion lymphoma, Cellular Types, Low Density Lipoprotein Receptor-Related Protein-1, Research Article, Signal Transduction, medicine.drug, Programmed cell death, MESH: Protein Transport, MESH: Calreticulin, Immunology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Line, 03 medical and health sciences, Immune system, Phagocytosis, Lymphoma, Primary Effusion, medicine, MESH: HSP90 Heat-Shock Proteins, Humans, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, MESH: Tyrphostins, Biology, 030304 developmental biology, MESH: Humans, MESH: Apoptosis, lcsh:R, MESH: Low Density Lipoprotein Receptor-Related Protein-1, Dendritic Cells, Immunotherapy, medicine.disease, MESH: Cell Line, Kinetics, Cancer cell, Cancer research, MESH: Antineoplastic Agents, lcsh:Q, Clinical Immunology, 030215 immunology
Abstract: International audience; To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients.
Published: 2012
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36. Investigations on the C1q–Calreticulin–Phosphatidylserine Interactions Yield New Insights into Apoptotic Cell Recognition

Author: Philippe Frachet, Gérard J. Arlaud, Mélanie Verneret, Christine Gaboriaud, Pascale Tacnet-Delorme, Helena Paidassi, Wai Li Ling, Karen Duus, Gunnar Houen, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Department of Autoimmunology, Statens Serum Institut [Copenhagen], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Small interfering RNA, MESH: Complement C1q, genetic structures, Cell, Apoptosis, MESH: Flow Cytometry, Cell Communication, HeLa, MESH: Recombinant Proteins, chemistry.chemical_compound, 0302 clinical medicine, Structural Biology, MESH: RNA, Small Interfering, RNA, Small Interfering, Receptor, MESH: Phagocytosis, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Phosphatidylserine, MESH: Phosphatidylserines, Flow Cytometry, Ligand (biochemistry), Recombinant Proteins, Cell biology, MESH: Surface Plasmon Resonance, medicine.anatomical_structure, cardiovascular system, MESH: Membrane Proteins, Protein Binding, circulatory and respiratory physiology, MESH: Calreticulin, Blotting, Western, chemical and pharmacologic phenomena, Phosphatidylserines, Biology, 03 medical and health sciences, Phagocytosis, MESH: Cell Communication, medicine, Humans, MESH: Blotting, Western, MESH: Protein Binding, cardiovascular diseases, Molecular Biology, 030304 developmental biology, MESH: Humans, Complement C1q, MESH: Apoptosis, Membrane Proteins, Surface Plasmon Resonance, biology.organism_classification, Molecular biology, chemistry, MESH: HeLa Cells, biology.protein, Calreticulin, HeLa Cells, 030215 immunology
Abstract: International audience; Both C1q and calreticulin (CRT) are involved in the recognition of apoptotic cells. CRT was initially characterized as a receptor for the C1q collagen-like fragment (CLF), whereas C1q was shown to bind apoptotic cells through its globular region (GR). Using purified CRT and recombinant CRT domains, we now provide unambiguous experimental evidence that, in addition to its CLF, the C1q GR also binds CRT and that both types of interactions are mediated by the CRT globular domain. Surface plasmon resonance analyses revealed that the C1q CLF and GR domains each bind individually to immobilized CRT and its globular domain with K(D) values of (2.6-8.3) × 10(-7) M. Further evidence that CRT binds to the C1q GR was obtained by electron microscopy. The role of CRT in the recognition of apoptotic HeLa cells by C1q was analyzed. The C1q GR partially colocalized with CRT on the surface of early apoptotic cells, and siRNA (small interfering RNA)-induced CRT deficiency resulted in increased apoptotic cell binding to C1q. The interaction between CRT and phosphatidylserine (PS), a known C1q ligand on apoptotic cells, was also investigated. The polar head of PS was shown to bind to CRT with a 10-fold higher affinity (K(D)=1.5 × 10(-5) M) than that determined for C1q, and, accordingly, the C1q GR-PS interaction was impaired in the presence of CRT. Together, these observations indicate that CRT, C1q, and PS are all closely involved in the uptake of apoptotic cells and strongly suggest a combinatorial role of these three molecules in the recognition step.
Published: 2011
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37. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways

Author: Chinetti-Gbaguidi, Giulia, Baron, Morgane, Bouhlel, Mohamed Amine, Vanhoutte, Jonathan, Copin, Corinne, Sebti, Yasmine, Derudas, Bruno, Mayi, Thérèse, Bories, Gael, Tailleux, Anne, Haulon, Stéphane, Zawadzki, Christophe, Jude, Brigitte, Staels, Bart, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), 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-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hémostase et pathologie cardiovasculaire, and EA2693-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé
Subjects: MESH: Cell Differentiation, MESH: Humans, MESH: Genetic Predisposition to Disease, nuclear receptors, cholesterol, MESH: Macrophages, Atherosclerosis, macrophages, MESH: Leukocytes, Mononuclear, MESH: Cholesterol, MESH: Orphan Nuclear Receptors, MESH: PPAR gamma, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Plaque, Atherosclerotic, MESH: Phagocytosis, MESH: Cells, Cultured
Abstract: International audience; RATIONALE: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an "alternative" M2 phenotype. OBJECTIVE: We previously reported the presence of CD68(+) mannose receptor (MR)(+) M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68(+)MR(+) macrophages is still unknown. METHODS AND RESULTS: Histological analysis revealed that CD68(+)MR(+) macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68(+)MR(-) macrophages. Interleukin (IL)-4-polarized CD68(+)MR(+) macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68(+)MR(+) macrophages. By contrast, CD68(+)MR(+) macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. CONCLUSIONS: These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.
Published: 2011
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38. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways

Author: Chinetti-Gbaguidi, Giulia, Baron, Morgane, Bouhlel, Mohamed Amine, Vanhoutte, Jonathan, Copin, Corinne, Sebti, Yasmine, Derudas, Bruno, Mayi, Thérèse, Bories, Gael, Tailleux, Anne, Haulon, Stéphane, Zawadzki, Christophe, Jude, Brigitte, Staels, Bart, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), 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-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hémostase et pathologie cardiovasculaire, EA2693-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, and Derudas, Marie-Hélène
Subjects: MESH: Cell Differentiation, MESH: Humans, MESH: Genetic Predisposition to Disease, nuclear receptors, cholesterol, MESH: Macrophages, Atherosclerosis, macrophages, MESH: Leukocytes, Mononuclear, MESH: Cholesterol, MESH: Orphan Nuclear Receptors, MESH: PPAR gamma, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Plaque, Atherosclerotic, MESH: Phagocytosis, MESH: Cells, Cultured
Abstract: International audience; RATIONALE: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an "alternative" M2 phenotype. OBJECTIVE: We previously reported the presence of CD68(+) mannose receptor (MR)(+) M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68(+)MR(+) macrophages is still unknown. METHODS AND RESULTS: Histological analysis revealed that CD68(+)MR(+) macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68(+)MR(-) macrophages. Interleukin (IL)-4-polarized CD68(+)MR(+) macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68(+)MR(+) macrophages. By contrast, CD68(+)MR(+) macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. CONCLUSIONS: These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.
Published: 2011
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39. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways.: Atherosclerotic plaque alternative macrophages

Author: Corinne Copin, Bruno Derudas, Giulia Chinetti-Gbaguidi, Jonathan Vanhoutte, Brigitte Jude, Bart Staels, Gael Bories, Christophe Zawadzki, Stephane Haulon, Anne Tailleux, Yasmine Sebti, Mohamed Amine Bouhlel, Thérèse Hèrvée Mayi, Morgane Baron, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), 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-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hémostase et pathologie cardiovasculaire, and EA2693-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé
Subjects: Apolipoprotein E, MESH: Cell Differentiation, Physiology, nuclear receptors, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, MESH: Cholesterol, Phagocytosis, Lipid droplet, Humans, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Plaque, Atherosclerotic, Liver X receptor, MESH: Phagocytosis, Cells, Cultured, 030304 developmental biology, Liver X Receptors, 0303 health sciences, MESH: Humans, biology, CD68, MESH: Genetic Predisposition to Disease, Interleukin, cholesterol, MESH: Macrophages, Cell Differentiation, Orphan Nuclear Receptors, Atherosclerosis, Plaque, Atherosclerotic, Cell biology, macrophages, PPAR gamma, MESH: Leukocytes, Mononuclear, Biochemistry, MESH: Orphan Nuclear Receptors, MESH: PPAR gamma, Monocyte differentiation, ABCA1, biology.protein, Leukocytes, Mononuclear, Cardiology and Cardiovascular Medicine, Mannose receptor, MESH: Cells, Cultured
Abstract: Rationale: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an “alternative” M2 phenotype. Objective: We previously reported the presence of CD68 + mannose receptor (MR) + M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68 + MR + macrophages is still unknown. Methods and Results: Histological analysis revealed that CD68 + MR + macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68 + MR − macrophages. Interleukin (IL)-4–polarized CD68 + MR + macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68 + MR + macrophages. By contrast, CD68 + MR + macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. Conclusions: These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.
Published: 2011
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40. Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis

Author: Jean-Christophe Simard, Denis Girard, Marie-Michelle Simon, Philippe A. Tessier, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Faculté de Médecine, and Université Laval [Québec] (ULaval)
Subjects: Blood Bactericidal Activity, MESH: Enzyme Activation, Neutrophils, Phagocytosis, Immunology, Syk, CD16, MESH: Neutrophils, MESH: Protein-Tyrosine Kinases, S100A9, Microbiology, Proinflammatory cytokine, MESH: Receptors, Pattern Recognition, Phosphatidylinositol 3-Kinases, MESH: Intracellular Signaling Peptides and Proteins, Escherichia coli, MESH: Calgranulin B, Immunology and Allergy, Calgranulin B, Humans, Syk Kinase, MESH: Phagocytosis, chemistry.chemical_classification, Mitogen-Activated Protein Kinase 1, Reactive oxygen species, NADPH oxidase, Mitogen-Activated Protein Kinase 3, MESH: Humans, biology, MESH: Proto-Oncogene Proteins c-akt, MESH: Escherichia coli, MESH: Blood Bactericidal Activity, MESH: Host-Pathogen Interactions, Intracellular Signaling Peptides and Proteins, Damage-associated molecular pattern, MESH: Reactive Oxygen Species, Protein-Tyrosine Kinases, Enzyme Activation, chemistry, MESH: Phosphatidylinositol 3-Kinases, Receptors, Pattern Recognition, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Host-Pathogen Interactions, biology.protein, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, MESH: Mitogen-Activated Protein Kinase 3, MESH: Mitogen-Activated Protein Kinase 1
Abstract: The damage-associated molecular-pattern S100A9 is found at inflammatory sites in infections and various autoimmune diseases. It is released at very high concentrations in the extracellular milieu by activated neutrophils and monocytes in response to various agents. This proinflammatory protein is found in infected mucosae and tissue abscesses where it acts notably as a potent neutrophil activator. In this study, we examined the role of S100A9 in the control of infections. S100A9 was found to increase human neutrophil bactericidal activity toward Escherichia coli. Although S100A9 induced the accumulation of reactive oxygen species over time through the activation of NADPH oxidase, its antimicrobial activity was mediated mainly by enhancing the efficiency of neutrophil phagocytosis. Interestingly, S100A9 did not act by increasing cell surface expression of CD16, CD32, or CD64 in neutrophils, indicating that its biological effect in FcR-mediated phagocytosis is independent of upregulation of FcγR levels. However, S100A9-induced phagocytic activity required the phosphorylation of Erk1/2, Akt, and Syk. Taken together, our results demonstrate that S100A9 stimulates neutrophil microbicidal activity by promoting phagocytosis.
Published: 2011
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41. Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections

Author: Jessica Quintin, Marie-Celine Lafarge, Nadine T. Nehme, Christine Kocks, Dominique Ferrandon, Jeannie T. Lee, Ju Hyun Cho, Jessica, Quintin, Réponse immunitaire et developpement chez les insectes (RIDI - UPR 9002), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV]Life Sciences [q-bio], Immunology/Innate Immunity, lcsh:Medicine, MESH: Gram-Positive Bacteria, Infectious Diseases/Bacterial Infections, MESH: Staphylococcus aureus, Enterococcus faecalis, Macrophage, Drosophila Proteins, MESH: Animals, MESH: Immunity, Humoral, lcsh:Science, MESH: Phagocytosis, MESH: Opsonin Proteins, MESH: Receptors, Cell Surface, Immunity, Cellular, Multidisciplinary, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Pattern recognition receptor, MESH: Antimicrobial Cationic Peptides, Opsonin Proteins, [SDV] Life Sciences [q-bio], Micrococcus luteus, Drosophila melanogaster, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Research Article, Signal Transduction, MESH: Enterococcus faecalis, Staphylococcus aureus, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Drosophila Proteins, Phagocytosis, Antimicrobial peptides, MESH: Carrier Proteins, Receptors, Cell Surface, Gram-Positive Bacteria, Microbiology, MESH: Drosophila melanogaster, MESH: Immunity, Cellular, Immune system, Immunity, Animals, Gram-Positive Bacterial Infections, Innate immune system, lcsh:R, MESH: Host-Pathogen Interactions, fungi, Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1], biology.organism_classification, Immunity, Innate, Immunity, Humoral, MESH: Solubility, Solubility, Immunology/Immune Response, lcsh:Q, MESH: Gram-Positive Bacterial Infections, Carrier Proteins, MESH: Micrococcus luteus, Antimicrobial Cationic Peptides
Abstract: Contains fulltext : 96277.pdf (Publisher’s version ) (Open Access) BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.
Published: 2011
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42. Effects of age, gender and time on receptor expression and anti-Aspergillus functions of human phagocytes

Author: Hervé Pelloux, C. Rolland, Jean Boutonnat, Gaelle Bal, Jean Paul Brion, Magali Hypolite, Renée Grillot, Chantal Dumestre-Pérard, Rose-Laurence Bertini, Delphine Aldebert, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de parasitologie-mycologie, CHU Grenoble, Maladie Infectieuse, Service de Médecine Interne et Maladies Infectieuses, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Receptor expression, MESH: Phagocytes, 0302 clinical medicine, Receptor, MESH: Phagocytosis, MESH: Antigens, CD, Immunologic Surveillance, Immune adherence reaction, 0303 health sciences, Phagocytes, Sex Characteristics, MESH: Middle Aged, Age Factors, MESH: Reactive Oxygen Species, Middle Aged, 3. Good health, Respiratory burst, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, MESH: Immunity, Innate, Female, MESH: Aspergillus fumigatus, MESH: Sex Characteristics, Adult, Antigens, Fungal, CD14, Immunology, Biology, Granulocyte, In Vitro Techniques, 03 medical and health sciences, Young Adult, Immune system, Phagocytosis, Antigens, CD, medicine, Humans, 030304 developmental biology, MESH: Antigens, Fungal, MESH: Immunologic Surveillance, MESH: Age Factors, Innate immune system, MESH: Humans, Aspergillus fumigatus, MESH: Adult, MESH: Male, Immunity, Innate, Reactive Oxygen Species, MESH: Female, 030215 immunology
Abstract: International audience; Phagocytes play a central role in immune defense. Their dysfunction predisposes to infections. This study determined the expression level of nine receptors involved in Aspergillus immune response as well as the values of phagocytosis and production of radical oxygen species after Aspergillus stimulation, in a healthy adult population. The expression values of the CD11b, CD11c, CD14, CD18, CD35, CD181, CD182, CD282 and CD284 receptors on peripheral human monocytes and granulocytes was established. A heterogenous expression of the CD282 on granulocytes was observed as CD181, CD182 and CD284 on monocytes. Similarly, we observed considerable variation in the expression of these receptors over time. Only CD282 on granulocytes varied with sex. No variation with age was observed. Adherence of Aspergillus conidia to phagocytes was dependent of individual, sex, age and time. A better characterization of these innate immunity parameters is necessary to develop in the future an immunologic surveillance strategy for transplant recipients.
Published: 2010
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43. Immunocompetence and alterations in hepatic gene expression in rainbow trout exposed to CdS/CdTe quantum dots

Author: G. van Aggelen, L. Yu, François Gagné, Michel Fournier, Heather L. Osachoff, Christian Gagnon, M. Fortier, Rachel C. Skirrow, Fluvial Ecosystem Research, Aquatic Ecosystem Research Protection, Water Science and Technology, Environment and Climate Change Canada, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Pacific and Yukon Laboratory for Environmental Testing, and Water Science and Technology
Subjects: Gene Expression, 010501 environmental sciences, Kidney, 01 natural sciences, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, Leukocyte Count, Gene expression, Metallothionein, Inducer, MESH: Animals, MESH: Phagocytosis, chemistry.chemical_classification, 0303 health sciences, Cadmium, biology, General Medicine, MESH: Quantum Dots, MESH: Water Pollutants, Chemical, Biochemistry, Liver, MESH: Tellurium, MESH: Oncorhynchus mykiss, Oncorhynchus mykiss, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Immunocompetence, Tellurium, Fish Proteins, MESH: Gene Expression, MESH: Cadmium, chemistry.chemical_element, Management, Monitoring, Policy and Law, 03 medical and health sciences, Vitellogenin, Phagocytosis, Quantum Dots, MESH: Fish Proteins, Animals, 14. Life underwater, 030304 developmental biology, 0105 earth and related environmental sciences, Reactive oxygen species, Dose-Response Relationship, Drug, Public Health, Environmental and Occupational Health, MESH: Kidney, MESH: Immunocompetence, chemistry, MESH: Leukocyte Count, Immunology, biology.protein, Xenobiotic, Water Pollutants, Chemical, MESH: Liver
Abstract: International audience; Cadmium (Cd) tellurium quantum dots (QDs) are long-lived fluorescent nanocrystals that have the ability to produce potentially toxic reactive oxygen species at the surface of the nanoparticle and release toxic cadmium ions. The purpose of this study was to examine the sublethal effects of CdS/CdTe QDs and dissolved Cd on the immune system of rainbow trout. Changes in hepatic gene expression were also monitored to provide insight on the mode of action of both forms of cadmium. Oncorhynchus mykiss fish were exposed to increasing concentrations of CdS/CdTe or dissolved Cd (CdSO(4)) for 48 h at 15 degrees C. The anterior head kidney was analyzed for leukocyte count, viability and phagocytic activity. The livers were harvested and prepared for gene expression analysis using a DNA microarray comprised of 207 stress-related genes. An analysis of total Cd in the aquarium water revealed that the nominal concentrations corresponded well to the actual concentrations and that a small proportion (0.4%) of Cd in the QDs was found in the dissolved fraction. Exposure to QDs led to significant reductions in leukocyte counts, viability and both resting and active phagocytic activity. On a mass concentration basis, QDs were more potent than dissolved Cd in suppressing immunocompetence in rainbow trout. The analysis revealed that both forms of Cd were strong inducers of metallothionein and CP2K1 gene expressions, which are respectively involved in metal detoxification processes and xenobiotic transformation/inflammation conditions. The analysis revealed different modes of action for each form of Cd. For QDs, 25 genes specific to QDs and related to the immune endpoints were found. The genes were involved in inflammation, xenobiotic biotransformation and endocrine system (including the induction of vitellogenin and its receptor). The effect for dissolved Cd was narrower than for QDs, with 9 genes specific to dissolved Cd being strongly correlated with the observed effects on immunocompetence. The involved genes were binding and transport of various solutes (urea, sodium, potassium) and the complement system. The present study revealed that each form of Cd produced a different pattern of gene expression and lowered fish immunocompetence.
Published: 2010
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44. Cell surface of Lactococcus lactis is covered by a protective polysaccharide pellicle

Author: Saulius Kulakauskas, Irina Sadovskaya, Patrick Trieu-Cuot, Yves F. Dufrêne, Elena Bidnenko, Evgeny Vinogradov, Christine Péchoux, Marie-Pierre Chapot-Chartier, Pascal Hols, Michel-Yves Mistou, Pascal Courtin, Sylviane Furlan, Guillaume Andre, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, National Research Council of Canada (NRC), Equipe APA, Université du Littoral Côte d'Opale (ULCO), Institut des Sciences de la Vie, Université Catholique de Louvain (UCL), Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génomique et Physiologie de la Lactation (GPL), Institut National de la Recherche Agronomique (INRA), UCL - SST/IMCN/BSMA - Bio and soft matter, UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries, UCL - SST/IMCN - Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain = Catholic University of Louvain (UCL), Unité de recherche génomique et physiologie de la lactation (GPL), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Bacterial capsule, Cell, Microscopy, Atomic Force, Biochemistry, Bacterial Adhesion, chemistry.chemical_compound, Cell Wall, MESH: Polysaccharides, Bacterial, MESH: Phagocytosis, MESH: Bacterial Proteins, Cells, Cultured, bactérie, chemistry.chemical_classification, MESH: Microscopy, Atomic Force, 0303 health sciences, biology, Polysaccharides, Bacterial, microscopie électronique, Chromosomes, Bacterial, ATOMIC-FORCE MICROSCOPY, GRAM-POSITIVE BACTERIA, COMPLETE GENOME, LACTOCOCCUS LACTIS, POLYSACCHARIDE, ultrastructure, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Mutagenesis, Site-Directed, medicine.anatomical_structure, Carbohydrate Sequence, Cell envelope, MESH: Cells, Cultured, MESH: Chromosomes, Bacterial, MESH: Mutation, MESH: Microscopy, Electron, Scanning, Molecular Sequence Data, Polysaccharide, Microbiology, Cell wall, 03 medical and health sciences, MESH: Cell Wall, Bacterial Proteins, Phagocytosis, MESH: Bacterial Capsules, medicine, MESH: Bacterial Adhesion, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Bacterial Capsules, 030304 developmental biology, MESH: Carbohydrate Sequence, MESH: Molecular Sequence Data, 030306 microbiology, Macrophages, Lactococcus lactis, MESH: Macrophages, Cell Biology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, chemistry, MESH: Lactococcus lactis, Mutation, Microscopy, Electron, Scanning, Mutagenesis, Site-Directed, Biophysics, Peptidoglycan, Bacteria
Abstract: In Gram-positive bacteria, the functional role of surface polysaccharides (PS) that are not of capsular nature remains poorly understood. Here, we report the presence of a novel cell wall PS pellicle on the surface of Lactococcus lactis. Spontaneous PS-negative mutants were selected using semi-liquid growth conditions, and all mutations were mapped in a single chromosomal locus coding for PS biosynthesis. PS molecules were shown to be composed of hexasaccharide phosphate repeating units that are distinct from other bacterial PS. Using complementary atomic force and transmission electron microscopy techniques, we showed that the PS layer forms an outer pellicle surrounding the cell. Notably, we found that this cell wall layer confers a protective barrier against host phagocytosis by murine macrophages. Altogether, our results suggest that the PS pellicle could represent a new cell envelope structural component of Gram-positive bacteria.
Published: 2010
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45. Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion

Author: Siamon Gordon, Audrey Varin, Georges Herbein, Subhankar Mukhopadhyay, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: MESH: Signal Transduction, MESH: Interleukin-13, Time Factors, medicine.medical_treatment, Neisseria meningitidis, Serogroup B, Biochemistry, MESH: Mice, Knockout, Mice, Phagocytes, Granulocytes, and Myelopoiesis, 0302 clinical medicine, Macrophage, MESH: Animals, Phosphorylation, Receptors, Immunologic, MESH: Phagocytosis, MESH: Receptors, Cell Surface, Mice, Knockout, 0303 health sciences, Interleukin-13, MESH: Macrophage Activation, Hematology, 3. Good health, Macrophage receptor with collagenous structure, Cytokine, Interleukin 13, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Macrophages, Peritoneal, MESH: Myeloid Differentiation Factor 88, Signal Transduction, Phagocytosis, Immunology, Receptors, Cell Surface, Biology, Microbiology, Proinflammatory cytokine, 03 medical and health sciences, Th2 Cells, MESH: Th2 Cells, MESH: Neisseria meningitidis, Serogroup B, medicine, Animals, Scavenger receptor, MESH: Receptors, Immunologic, MESH: Mice, 030304 developmental biology, MESH: Phosphorylation, MESH: Proto-Oncogene Proteins c-akt, MESH: Time Factors, Cell Biology, MESH: Interleukin-4, Macrophage Activation, Myeloid Differentiation Factor 88, Macrophages, Peritoneal, Cytokine secretion, Interleukin-4, Proto-Oncogene Proteins c-akt, 030215 immunology
Abstract: Alternatively activated macrophages play an important role in host defense in the context of a T helper type 2 (Th2) microenvironment such as parasitic infection. However, the role of these macrophages during secondary challenge with Th1 pathogens is poorly defined. In this study, thioglycollate-elicited mouse peritoneal macrophages were treated with interleukin-4 (IL-4) or IL-13 in vitro and challenged with Neisseria meningitidis. After 8 to 12 hours of IL-4 pretreatment, the nonopsonic phagocytic uptake of N meningitidis was markedly reduced, depending on the common IL-4Rα chain, but independent of Scavenger receptor A and macrophage receptor with collagenous structure (MARCO), 2 known receptors for N meningitidis. Inhibition of phagocytosis extended to several other microbial particles, zymosan, and other bacteria. Concomitantly, IL-4 potentiated the secretion of proinflammatory cytokines, after additional bacterial stimulation, which depended on the MyD88 signaling pathway. Similar results were obtained after intraperitoneal stimulation of IL-4 and N meningitidis in vivo. Further in vitro studies showed a striking correlation with inhibition of Akt phosphorylation and stimulation of the mitogen-activated protein kinase pathway; inhibition of phagocytosis was associated with inhibition of phagosome formation. These findings are relevant to host defense in mixed infections within a Th2 microenvironment and shed light on immunologic functions associated with alternative priming and full activation of macrophages.
Published: 2010
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46. Listeria monocytogenes Internalin and E-cadherin: From Bench to Bedside

Author: Matteo Bonazzi, Marc Lecuit, Pascale Cossart, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and DIAKITE, andrée
Subjects: [SDV]Life Sciences [q-bio], medicine.disease_cause, MESH: Listeria monocytogenes, MESH: Cadherins, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, MESH: Models, Genetic, Receptor, MESH: Phagocytosis, MESH: Bacterial Proteins, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030302 biochemistry & molecular biology, Meningoencephalitis, Cadherins, Endocytosis, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Endocytosis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Perspectives, MESH: Mice, Transgenic, Phagocytosis, Mice, Transgenic, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Bacterial Proteins, Species Specificity, medicine, Animals, Humans, MESH: Species Specificity, Internalin, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Mice, 030304 developmental biology, MESH: Humans, Models, Genetic, Cadherin, MESH: Models, Biological, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bench to bedside, Listeria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Listeria monocytogenes is a Gram-positive bacterium responsible for a severe infection associated with different clinical features (gastroenteritis, meningoencephalitis, and abortion in pregnant women). These pathologies are caused by the unusual capacity of the bacterium to cross three host barriers during infection and to invade nonphagocytic cells. To invade host cells, Listeria uses two proteins, InlA and InlB, which have specific receptors on the host-cell surface, E-cadherin and Met, respectively. Here, we discuss the specificity of the InlA-E-cadherin interaction, the signaling cascade activated on E-cadherin engagement by InlA, and the role of InlA and E-cadherin in the breaching of host barriers and the dissemination of the infection.
Published: 2009
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47. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco

Author: Michel Sautarel, Alain Taïeb, Franck Boralevi, Marie José Stasia, Fanny Morice-Picard, Rahima Mostefai, John A. McGrath, Didier Lacombe, Dermatologie pédiatrique - Bordeaux, CHU Bordeaux [Bordeaux], Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Department of Pediatrics [Libourne], Centre Hospitalier Libourne, and Supported by the GENESKIN coordination action EU FP6 LSHB-CT-2005-512117
Subjects: Lung Diseases, Male, Neutrophils, DNA Mutational Analysis, MESH: Neutrophils, MESH: Rothmund-Thomson Syndrome, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, dyskeratosis congenital, cystic fibrosis, MESH: Lung Diseases, Consanguinity, MESH: Child, Medicine, MESH: Syndrome, MESH: DNA Mutational Analysis, MESH: Phagocytosis, Child, Rothmund–Thomson syndrome, Genetics (clinical), Skin, 0303 health sciences, 030305 genetics & heredity, Rothmund-Thomson Syndrome, Syndrome, MESH: Infant, Dyskeratosis, 3. Good health, Pedigree, Morocco, Child, Preschool, Female, medicine.medical_specialty, Neutropenia, MESH: Neutropenia, MESH: Pedigree, Poikiloderma, Genes, Recessive, Kindler syndrome, Diagnosis, Differential, 03 medical and health sciences, MESH: Skin, Phagocytosis, Pachyonychia, MESH: Diagnosis, Differential, Internal medicine, Rothmund- Thomson syndrome, Genetics, Humans, Pigmentation disorder, MESH: Genes, Recessive, 030304 developmental biology, MESH: Consanguinity, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, medicine.disease, Dermatology, MESH: Male, Palmoplantar keratoderma, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Morocco, business, MESH: Female, Dyskeratosis congenita
Abstract: International audience; Three siblings from Morocco consanguineous family presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Several broncho-pulmonary infectious episodes complicated the evolution, and cystic fibrosis was first considered on the basis of repeated abnormal sweat chloride tests but not confirmed by molecular analyses. This autosomal recessive disorder matches that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians (OMIM 604173). It is discussed within the group of the major hereditary poikiloderma disorders, that is, Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome.
Published: 2008
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48. TM9SF4 is required for Drosophila cellular immunity via cell adhesion and phagocytosis

Author: Evelyne Bergeret, Didier Grunwald, Emmanuel Taillebourg, Michael Williams, Franz Bruckert, Pierre Cosson, Dominique Thevenon, Jackie Perrin, Marie-Odile Fauvarque, Elodie Engel, Transduction du signal : signalisation calcium, phosphorylation et inflammation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Biological and Environmental Sciences, University of Aberdeen, ANTE-INSERM U836, équipe 4, Muscles et pathologies, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Minatec, Institut Polytechnique de Grenoble - Grenoble Institute of Technology, Département de Physiologie Cellulaire et Métabolisme, Université de Genève = University of Geneva (UNIGE), Université de Genève (UNIGE), and Fauvarque, Marie-Odile
Subjects: MESH: Signal Transduction, Cellular immunity, Hemocytes, Mammals/genetics/immunology, Mutant, MESH: Dictyostelium, Signal Transduction/genetics/immunology, MESH: Phagocytes, Dictyostelium discoideum, 0302 clinical medicine, MESH: Staphylococcus aureus, Dictyostelium, MESH: Animals, Larva/genetics/immunology/microbiology, Hemocytes/cytology/immunology, MESH: Phagocytosis, Mammals, 0303 health sciences, Phagocytes, Phagocytes/cytology/immunology, Schneider 2 cells, MESH: Escherichia coli, Immunity, Innate/physiology, Cell biology, Cell Adhesion/genetics/immunology, Drosophila melanogaster, Larva, MESH: Immunity, Innate, MESH: Membrane Proteins, Staphylococcus aureus/immunology, Dictyostelium/genetics/immunology, Signal Transduction, Staphylococcus aureus, Mutation/genetics/immunology, MESH: Mutation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Mammals, Phagocytosis/genetics/immunology, Cell Line, MESH: Cell Adhesion, MESH: Drosophila melanogaster, 03 medical and health sciences, Phagocytosis, Cell Adhesion, Escherichia coli, Animals, ddc:612, Cell adhesion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Innate immune system, Escherichia coli/immunology, fungi, Membrane Proteins/genetics/immunology, Membrane Proteins, MESH: Hemocytes, Cell Biology, biology.organism_classification, Actin cytoskeleton, Immunity, Innate, MESH: Cell Line, Mutation, MESH: Larva, 030217 neurology & neurosurgery
Abstract: International audience; Nonaspanins are characterised by a large N-terminal extracellular domain and nine putative transmembrane domains. This evolutionarily conserved family comprises three members in Dictyostelium discoideum (Phg1A, Phg1B and Phg1C) and Drosophila melanogaster, and four in mammals (TM9SF1-TM9SF4), the function of which is essentially unknown. Genetic studies in Dictyostelium demonstrated that Phg1A is required for cell adhesion and phagocytosis. We created Phg1A/TM9SF4-null mutant flies and showed that they were sensitive to pathogenic Gram-negative, but not Gram-positive, bacteria. This increased sensitivity was not due to impaired Toll or Imd signalling, but rather to a defective cellular immune response. TM9SF4-null larval macrophages phagocytosed Gram-negative E. coli inefficiently, although Gram-positive S. aureus were phagocytosed normally. Mutant larvae also had a decreased wasp egg encapsulation rate, a process requiring haemocyte-dependent adhesion to parasitoids. Defective cellular immunity was coupled to morphological and adhesion defects in mutant larval haemocytes, which had an abnormal actin cytoskeleton. TM9SF4, and its closest paralogue TM9SF2, were both required for bacterial internalisation in S2 cells, where they displayed partial redundancy. Our study highlights the contribution of phagocytes to host defence in an organism possessing a complex innate immune response and suggests an evolutionarily conserved function of TM9SF4 in eukaryotic phagocytes.
Published: 2008
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49. [Secreted exosomes from reticulocytes express an eat-me signal]

Author: Blanc, Lionel, Vidal, Michel, Dynamique des interactions membranaires normales et pathologiques (DIMNP), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)
Subjects: MESH: Signal Transduction, MESH: Humans, MESH: Apoptosis, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Phagocytosis, MESH: Reticulocytes, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008
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50. Effects of 16 pure hydrocarbons and two oils on haemocyte and haemolymphatic parameters in the Pacific oyster, Crassostrea gigas (Thunberg)

Author: Béatrice Gagnaire, Tristan Renault, Anne Bado-Nilles, Stéphane Le Floch, Hélène Thomas-Guyon, Laboratoire de Ploufragan - Plouzané, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratory of Radionuclide Ecotoxicology (PRP-ENV/SERIS/LECO), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Centre de documentation de recherche et d'expérimentations sur les pollutions accidentelles des eaux (Cedre), Cedre, Laboratoire de Génétique et Pathologie (LGP), and Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)
Subjects: Chrysene, Hemocytes, Time Factors, 010501 environmental sciences, Toxicology, 01 natural sciences, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, Hemolymph, Pacific oyster, MESH: Animals, Flow cytometry, Polycyclic Aromatic Hydrocarbons, MESH: Phagocytosis, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, biology, General Medicine, MESH: Water Pollutants, Chemical, Spectrophotometry, Environmental chemistry, MESH: Oils, Pyrene, Crassostrea, Fluorene, 03 medical and health sciences, MESH: Polycyclic Hydrocarbons, Aromatic, PAHs, Phagocytosis, Animals, 14. Life underwater, 030304 developmental biology, 0105 earth and related environmental sciences, Fluoranthene, Anthracene, Toxicity, Dose-Response Relationship, Drug, MESH: Hemolymph, MESH: Time Factors, MESH: Hemocytes, Phenanthrene, biology.organism_classification, MESH: Crassostrea, chemistry, 13. Climate action, Haemocyte activity, Oils, Water Pollutants, Chemical
Abstract: The in vitro effects of polycyclic aromatic hydrocarbons (PAHs) on haemocyte and haemolymphatic parameters of the Pacific oyster, Crassostrea gigas, were tested using field concentrations (10(-7) and 10(-9) mg mL(-1)) observed in the Marennes-Oleron Basin (Charente-Maritime, France) and high concentrations (10(-3) and 10(-5) mg mL(-1)) observed during oil spills. As a first step, the effects of pollutants, after a 24 h contamination period, were monitored on individual and pooled haemolymph samples and similar results were observed for both sample types. In a second step, haemolymphs from 45 oysters were withdrawn and pooled. Eighteen pollutants were tested in vitro after a 4 and 24 h contamination period and 10 of them showed significant modulations of the five haemocyte parameters tested. Seven pollutants (fluorene, pyrene, anthracene, phenanthrene, chrysene, indeno[1,2,3-c,d]pyrene and heavy fuel oil (HFO)) induced a decrease in haemocyte mortality. Fluorene, pyrene and HFO significantly decreased phagocytosis activity. Percentage of non-specific esterase positive cells, phenoloxidase activity and lysosome presence were increased by naphthalene, benzo[b]fluoranthene and dibenz[a,h]anthracene, respectively. Modulation of immune parameters in the Pacific oyster by PAHs suggested that PAH pollution may be related to enhanced susceptibility to diseases. (C) 2008 Elsevier Ltd. All rights reserved.
Published: 2008
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