117 results on '"Schwartz-Cornil I"'
Search Results
2. Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV
- Author
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Niborski, V., Li, Y., Brennan, F., Lane, M., Torché, A.M., Remond, M., Bonneau, M., Riffault, S., Stirling, C., Hutchings, G., Takamatsu, H., Barnett, P., Charley, B., and Schwartz-Cornil, I.
- Published
- 2006
- Full Text
- View/download PDF
3. B-1-like cells exist in sheep. Characterization of their phenotype and behaviour
- Author
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CHEVALLIER, N., BERTHELEMY, M., LAINÉ, V., LE RHUN, D., FÉMÉNIA, F., POLACK, B., NAESSENS, J., LEVY, D., and SCHWARTZ-CORNIL, I.
- Published
- 1998
4. Pig as a biomedical model: Putting the porcine lung dendritic cells/macrophages network into light
- Author
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Maisonnasse, P., primary, Bouguyon, E., additional, Bourge, M., additional, Piton, G., additional, Ezquerra, A., additional, Deloizy, C., additional, Urien, C., additional, Leplat, J.-J., additional, Simon, G., additional, Chevalier, C., additional, Vincent-Naulleau, S., additional, Crisci, E., additional, Montoya, M., additional, Schwartz-Cornil, I., additional, and Bertho, N., additional
- Published
- 2017
- Full Text
- View/download PDF
5. The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model
- Author
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Maisonnasse, P, primary, Bouguyon, E, additional, Piton, G, additional, Ezquerra, A, additional, Urien, C, additional, Deloizy, C, additional, Bourge, M, additional, Leplat, J-J, additional, Simon, G, additional, Chevalier, C, additional, Vincent-Naulleau, S, additional, Crisci, E, additional, Montoya, M, additional, Schwartz-Cornil, I, additional, and Bertho, N, additional
- Published
- 2016
- Full Text
- View/download PDF
6. 118 COMPARISON OF TRANSCRIPTOME PROFILES FROM ENDOMETRIAL CARUNCLES AND PERIPHERAL BLOOD MONONUCLEAR CELLS REVEAL COMMON AND TISSUE-SPECIFIC BIOLOGICAL PROCESSES REGULATED AT IMPLANTATION IN SHEEP
- Author
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Mauffré, V., primary, Sandra, O., additional, Giraud-Delville, C., additional, Urien, C., additional, Jouneau, L., additional, Loup, B., additional, Valour, D., additional, Cotinot, C., additional, Schwartz-Cornil, I., additional, Grimard, B., additional, and Constant, F., additional
- Published
- 2015
- Full Text
- View/download PDF
7. Towards new vaccines for domestic animals: a conventional skin lymph ovine DC subset shares functional and transcriptomic properties with the cross-priming CD8alpha murine DC
- Author
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Contreras, Vanessa, Urien, Celine, Bonneau, M, Jouneau, Luc, Bertho, Nicolas, Amigorena, S, Savina, A, Dalod, Marc, Schwartz-Cornil, I, ProdInra, Migration, Inconnu, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), UE 1298 Unité Commune d'Expérimentation Animale, Institut Curie [Paris], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] ,[INFO] Computer Science [cs] ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2009
8. Plasmacytoid dendritic cells migrate in afferent skin lymph (Correction: vol 180, pg 5963, 2008)
- Author
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Pascale, F., Contreras, V., Bonneau, M., Courbet, A., Chilmonczyk, S., Bevilacqua, C., Eparaud, M., Niborski, V., Riffault, S., Balazuc, A.M., Foulon, E., Guzylack-Piriou, L., Riteau, B., Hope, J., Bertho, N., Charley, B., and Schwartz-Cornil, I.
- Published
- 2008
9. Présentation antigénique de Salmonella par des cellules dendritiques lymphatiques ovines d'origine cutanée et muqueuse
- Author
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Olivier, Michel, Le Vern, Yves, Kerboeuf, Dominique, Bonneau, M, Schwartz-Cornil, I, Guilloteau, Laurence, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Inconnu, and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2007
10. Effects of somatic cloning on the immune response in young and adult cattle
- Author
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Chavatte-Palmer, Pascale, Renard, Jean Paul, Servely, Jean Luc, Heyman, Yvan, Schwartz-Cornil, I, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), and Institut National de la Recherche Agronomique (INRA)
- Subjects
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] ,IMMUNOLOGIE ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2006
11. Rotavirus anti-VP6 secretory immunoglobulin a contributes to protection via intracellular neutralization but not via immune exclusion
- Author
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Corthésy, Blaise, Benureau, Yann, Perrier, Clémentine, Fourgeux, Cynthia, Parez, Nathalie, Greenberg, Harry, Schwartz-Cornil, I, Schwartz-Cornil, Isabelle, Centre Hospitalier Universitaire Vaudois (CHUV), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Departments of Medicine, and Microbiology and Immunology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Roche [Palo Alto], and Inconnu
- Subjects
Rotavirus ,Immunoglobulin A ,medicine.drug_class ,Immunology ,Biology ,Antibodies, Viral ,Virus Replication ,medicine.disease_cause ,Monoclonal antibody ,Microbiology ,Rotavirus Infections ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Neutralization Tests ,Virology ,medicine ,Animals ,Humans ,Antigens, Viral ,030304 developmental biology ,Mice, Inbred BALB C ,0303 health sciences ,Antibodies, Monoclonal ,3. Good health ,Intestines ,Transcytosis ,Viral replication ,Insect Science ,Immunoglobulin A, Secretory ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,biology.protein ,Pathogenesis and Immunity ,Capsid Proteins ,Caco-2 Cells ,Antibody ,030215 immunology - Abstract
Immunoglobulin A (IgA) monoclonal antibodies (MAbs) directed at the conserved inner core protein VP6 of rotavirus, such as the IgA7D9 MAb, provide protective immunity in adult and suckling mice when delivered systemically. While these antibodies do not have traditional in vitro neutralizing activity, they could mediate their antiviral activity either by interfering with the viral replication cycle along the IgA secretory pathway or by acting at mucosal surfaces as secretory IgA and excluding virus from target enterocytes. We sought to determine the critical step at which antirotaviral activity was initiated by the IgA7D9 MAb. The IgA7D9 MAb appeared to directly interact with purified triple-layer viral particles, as shown by immunoprecipitation and immunoblotting. However, protection was not conferred by passively feeding mice with the secretory IgA7D9 MAb. This indicates that the secretory IgA7D9 MAb does not confer protection by supplying immune exclusion activity in vivo. We next evaluated the capacity of polymeric IgA7D9 MAb to neutralize rotavirus intracellularly during transcytosis. We found that when polymeric IgA7D9 MAb was applied to the basolateral pole of polarized Caco-2 intestinal cells, it significantly reduced viral replication and prevented the loss of barrier function induced by apical exposure of the cell monolayer to rotavirus, supporting the conclusion that the antibody carries out its antiviral activity intracellularly. These findings identify a mechanism whereby the well-conserved immunodominant VP6 protein can function as a target for heterotypic antibodies and protective immunity.
- Published
- 2006
12. Enrichment for a SIRP negative dendritic cell subset in lymph draining the upper aero-digestive tract: potential implication for tolerance
- Author
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Epardaud, Mathieu, Bonneau, M, Payot, F, Howard, C, Schwartz-Cornil, I, Contrôle des maladies animales exotiques et émergentes (Cirad-EMVT-UPR 15 Contrôle des maladies), Département Elevage et médecine vétérinaire (Cirad-EMVT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Inconnu, and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2003
13. Aspects moléculaires de l'immunité antivirale
- Author
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Schwartz-Cornil, I., ProdInra, Migration, Unité mixte de recherche biologie moléculaire et immunologie parasitaires et fongiques, Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire - Alfort (ENVA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
- Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,VECTEUR ,GENETIQUE ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 1998
14. Mycobacterium bovisBCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis
- Author
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Ovchinnikova, O. A., primary, Berge, N., additional, Kang, C., additional, Urien, C., additional, Ketelhuth, D. F. J., additional, Pottier, J., additional, Drouet, L., additional, Hansson, G. K., additional, Marchal, G., additional, Bäck, M., additional, Schwartz-Cornil, I., additional, and Lagranderie, M., additional
- Published
- 2013
- Full Text
- View/download PDF
15. Two- and three-dimensional cell structures govern epidermal growth factor survival function in human bladder carcinoma cell lines
- Author
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Dangles, V., FEMENIA, F., Lainé, Véronique, Berthelemy, Madeleine, Le Rhun, Danielle, Poupon, M.F., Levy, Danielle, Schwartz-Cornil, I., Unité mixte de recherche biologie moléculaire et immunologie parasitaires et fongiques, Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ProdInra, Migration, and Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire - Alfort (ENVA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,CANCER - Abstract
1 tables 3 graph.; International audience
- Published
- 1997
16. Bovine immunodeficiency virus : facts and questions
- Author
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Belloc, Catherine, Polack, Bruno, Schwartz Cornil, I., Brownlie, J., Levy, Danielle, Schwartz, Isabelle, inconnu, Inconnu, Mount Sinai Hospital [Toronto, Canada] (MSH), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche biologie moléculaire et immunologie parasitaires et fongiques, Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Agence Française de Sécurité Sanitaire des Aliments (AFSSA)-École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
- Subjects
bovin ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV]Life Sciences [q-bio] ,viruses ,Cattle Diseases ,Genome, Viral ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Prevalence ,Animals ,ComputingMilieux_MISCELLANEOUS ,Repetitive Sequences, Nucleic Acid ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Lentivirus ,Immunologic Deficiency Syndromes ,Genetic Variation ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,virus pathogène ,VIROLOGIE ,[SDV] Life Sciences [q-bio] ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Médecine vétérinaire et santé animal ,déficience immunologique ,Lentivirus Infections ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cattle ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Veterinary medicine and animal Health ,virus de l'immunodéficience bovine ,Rabbits - Abstract
Bovine immunodeficiency virus (BIV) is a lentivirus whose serologic prevalence is worldwide. Little is known about its impact on animal health status, pathogenesis and mode of transmission. Understanding BIV biology implies isolation of new viral strains and long-term studies on experimentally-infected cows and surrogate hosts such as rabbits.
- Published
- 1996
17. Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells
- Author
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Muixi, L., primary, Contreras, V., additional, Collado, J. A., additional, Alexandre, Y., additional, Ballingall, K., additional, Bonneau, M., additional, Jaraquemada, D., additional, and Schwartz-Cornil, I., additional
- Published
- 2011
- Full Text
- View/download PDF
18. Abstract No. 181: Improvement of VX2 tumor model by transfection with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)
- Author
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Pascale, F.T., primary, Wassef, M., additional, Ghegediban, S., additional, Bonneau, M., additional, Bedouet, L., additional, Verret, V., additional, Schwartz-Cornil, I., additional, Namur, J., additional, and Laurent, A., additional
- Published
- 2011
- Full Text
- View/download PDF
19. Abstract No. 55: Tissular diffusion of ibuprofen from embolization beads
- Author
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Verret, V., primary, Bevilacqua, C., additional, Schwartz-Cornil, I., additional, Pelage, J., additional, Wassef, M., additional, Namur, J., additional, Bedouet, L., additional, Lewis, A., additional, Martin, P., additional, and Laurent, A., additional
- Published
- 2011
- Full Text
- View/download PDF
20. Plasmacytoid dendritic cells migrate in afferent skin lymph.
- Author
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Pascale, F., primary, Contreras, V., additional, Bonneau, M., additional, Courbet, A., additional, Chilmonczyk, S., additional, Bevilacqua, C., additional, Eparaud, M., additional, Niborski, V., additional, Riffault, S., additional, Balazuc, A.-M., additional, Foulon, E., additional, Guzylack-Piriou, L., additional, Riteau, B., additional, Hope, J., additional, Bertho, N., additional, Charley, B., additional, and Schwartz-Cornil, I., additional
- Published
- 2008
- Full Text
- View/download PDF
21. CD11b is an activation marker expressed on a large population of sheep peripheral blood B cells
- Author
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Chevallier, N., primary, Berthelemy, M., additional, Le Rhun, D., additional, Lainé, V., additional, Féménia, F., additional, Polack, B., additional, Levy, D., additional, and Schwartz-Cornil, I., additional
- Published
- 1997
- Full Text
- View/download PDF
22. Bovine leukaemia virus-induced lymphocytosis in sheep is associated with reduction of spontaneous B cell apoptosis.
- Author
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Schwartz-Cornil, I, primary, Berthelemy, M, additional, Levy, D, additional, Lainé, V, additional, Le Rhun, D, additional, Mateo, A, additional, Belloc, C, additional, and Chevallier, N, additional
- Published
- 1997
- Full Text
- View/download PDF
23. The immunoglobulin CH1 constant region modulates antigen binding affinity and functional activities of the broadly neutralizing 2F5 HIV specific antibody
- Author
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Shen Ruizhong, Schwartz-Cornil Isabelle, Drillet Anne-Sophie, Tudor Daniela, Smith Phillip D, and Bomsel Morgane
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2010
- Full Text
- View/download PDF
24. Issues and special features of animal health research
- Author
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Ducrot Christian, Bed'Hom Bertrand, Béringue Vincent, Coulon Jean-Baptiste, Fourichon Christine, Guérin Jean-Luc, Krebs Stéphane, Rainard Pascal, Schwartz-Cornil Isabelle, Torny Didier, Vayssier-Taussat Muriel, Zientara Stephan, Zundel Etienne, and Pineau Thierry
- Subjects
Veterinary medicine ,SF600-1100 - Abstract
Abstract In the rapidly changing context of research on animal health, INRA launched a collective discussion on the challenges facing the field, its distinguishing features, and synergies with biomedical research. As has been declared forcibly by the heads of WHO, FAO and OIE, the challenges facing animal health, beyond diseases transmissible to humans, are critically important and involve food security, agriculture economics, and the ensemble of economic activities associated with agriculture. There are in addition issues related to public health (zoonoses, xenobiotics, antimicrobial resistance), the environment, and animal welfare. Animal health research is distinguished by particular methodologies and scientific questions that stem from the specific biological features of domestic species and from animal husbandry practices. It generally does not explore the same scientific questions as research on human biology, even when the same pathogens are being studied, and the discipline is rooted in a very specific agricultural and economic context. Generic and methodological synergies nevertheless exist with biomedical research, particularly with regard to tools and biological models. Certain domestic species furthermore present more functional similarities with humans than laboratory rodents. The singularity of animal health research in relation to biomedical research should be taken into account in the organization, evaluation, and funding of the field through a policy that clearly recognizes the specific issues at stake. At the same time, the One Health approach should facilitate closer collaboration between biomedical and animal health research at the level of research teams and programmes.
- Published
- 2011
- Full Text
- View/download PDF
25. SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses.
- Author
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Vu Manh TP, Gouin C, De Wolf J, Jouneau L, Pascale F, Bevilacqua C, Ar Gouilh M, Da Costa B, Chevalier C, Glorion M, Hannouche L, Urien C, Estephan J, Magnan A, Le Guen M, Marquant Q, Descamps D, Dalod M, Schwartz-Cornil I, and Sage E
- Subjects
- Humans, Monocytes virology, Monocytes metabolism, Monocytes immunology, Male, Female, Single-Cell Analysis, Middle Aged, COVID-19 virology, COVID-19 immunology, SARS-CoV-2 physiology, Lung virology, Lung immunology, Lung pathology, Macrophages virology, Macrophages metabolism, Macrophages immunology, Macrophages, Alveolar virology, Macrophages, Alveolar immunology, Macrophages, Alveolar metabolism, Cytokines metabolism
- Abstract
Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
26. Prolonged dialysis during ex vivo lung perfusion promotes inflammatory responses.
- Author
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De Wolf J, Gouin C, Jouneau L, Glorion M, Premachandra A, Pascale F, Huriet M, Estephan J, Leplat JJ, Egidy G, Richard C, Gelin V, Urien C, Roux A, Le Guen M, Schwartz-Cornil I, and Sage E
- Subjects
- Swine, Animals, Perfusion methods, Organ Preservation methods, Renal Dialysis, Lung physiology, Lung Transplantation methods
- Abstract
Ex-vivo lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung. Here, we assessed the biological effects of a hemodialyzer during EVLP by performing biochemical and refined functional genomic analyses over a 12h procedure in a pig model. We found that dialysis stabilized electrolytic and metabolic parameters of the perfusate but enhanced the gene expression and protein accumulation of several inflammatory cytokines and promoted a genomic profile predicting higher endothelial activation already at 6h and higher immune cytokine signaling at 12h. Therefore, epuration of EVLP with a dialyzer, while correcting features of the perfusate composition and maintaining the respiratory function, promotes inflammatory responses in the tissue. This finding suggests that modifying the metabolite composition of the perfusate by dialysis during EVLP can have detrimental effects on the tissue response and that this strategy should not be transferred as such to the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 De Wolf, Gouin, Jouneau, Glorion, Premachandra, Pascale, Huriet, Estephan, Leplat, Egidy, Richard, Gelin, Urien, Roux, Le Guen, Schwartz-Cornil and Sage.)
- Published
- 2024
- Full Text
- View/download PDF
27. Differential early response of monocyte/macrophage subsets to intra-operative corticosteroid administration in lung transplantation.
- Author
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Glorion M, Pascale F, Huriet M, Estephan J, Gouin C, Urien C, Bourge M, Egidy G, Richard C, Gelin V, De Wolf J, Le Guen M, Magnan A, Roux A, Devillier P, Schwartz-Cornil I, and Sage E
- Subjects
- Animals, Swine, Myeloid Cells, Macrophages, Adrenal Cortex Hormones metabolism, Monocytes metabolism, Lung Transplantation
- Abstract
Introduction: Lung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known., Methods: To address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours., Results: Myeloid cells, i.e. granulocytes and monocytic cells including classical CD14
pos and non-classical/intermediate CD16pos cells, were the dominantly recruited subsets, with the latter upregulating the membrane expression of MHC class II and CD80/86 molecules. Whereas corticosteroids did not reduce the different cell subset recruitment, they potently dampened the MHC class II and CD80/86 expression on monocytic cells and not on alveolar macrophages. Besides, corticosteroids induced a temporary and partial anti-inflammatory gene profile depending on cytokines and monocyte/macrophage subsets., Discussion: This work documents the baseline effects of the standard-of-care corticosteroid treatment for early innate allo-responses. These insights will enable further optimization and improvement of lung transplantation outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Glorion, Pascale, Huriet, Estephan, Gouin, Urien, Bourge, Egidy, Richard, Gelin, De Wolf, Le Guen, Magnan, Roux, Devillier, Schwartz-Cornil and Sage.)- Published
- 2023
- Full Text
- View/download PDF
28. Cell type- and time-dependent biological responses in ex vivo perfused lung grafts.
- Author
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Gouin C, Vu Manh TP, Jouneau L, Bevilacqua C, De Wolf J, Glorion M, Hannouche L, Urien C, Estephan J, Roux A, Magnan A, Le Guen M, Da Costa B, Chevalier C, Descamps D, Schwartz-Cornil I, Dalod M, and Sage E
- Subjects
- Humans, Perfusion methods, Endothelial Cells, Lung physiology, Inflammation, CD8-Positive T-Lymphocytes, Lung Transplantation methods
- Abstract
In response to the increasing demand for lung transplantation, ex vivo lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs. However despite an expanding use in clinical practice, the responses of the different lung cell types to EVLP are not known. In order to advance our mechanistic understanding and establish a refine tool for improvement of EVLP, we conducted a pioneer study involving single cell RNA-seq on human lungs declined for transplantation. Functional enrichment analyses were performed upon integration of data sets generated at 4 h (clinical duration) and 10 h (prolonged duration) from two human lungs processed to EVLP. Pathways related to inflammation were predicted activated in epithelial and blood endothelial cells, in monocyte-derived macrophages and temporally at 4 h in alveolar macrophages. Pathways related to cytoskeleton signaling/organization were predicted reduced in most cell types mainly at 10 h. We identified a division of labor between cell types for the selected expression of cytokine and chemokine genes that varied according to time. Immune cells including CD4
+ and CD8+ T cells, NK cells, mast cells and conventional dendritic cells displayed gene expression patterns indicating blunted activation, already at 4 h in several instances and further more at 10 h. Therefore despite inducing inflammatory responses, EVLP appears to dampen the activation of major lung immune cell types, what may be beneficial to the outcome of transplantation. Our results also support that therapeutics approaches aiming at reducing inflammation upon EVLP should target both the alveolar and vascular compartments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gouin, Vu Manh, Jouneau, Bevilacqua, De Wolf, Glorion, Hannouche, Urien, Estephan, Roux, Magnan, Le Guen, Da Costa, Chevalier, Descamps, Schwartz-Cornil, Dalod and Sage.)- Published
- 2023
- Full Text
- View/download PDF
29. A cross-circulatory platform for monitoring innate allo-responses in lung grafts.
- Author
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Glorion M, Pascale F, Estephan J, Huriet M, Gouin C, Urien C, Blanc F, Rivière J, Richard C, Gelin V, De Wolf J, Le Guen M, Magnan A, Roux A, Schwartz-Cornil I, and Sage E
- Subjects
- Animals, Swine, Lung, Genes, MHC Class II, Perfusion, Lung Transplantation
- Abstract
Lung transplantation is the only curative option for end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Although experimental evidences have shown that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms involved is limited. We established a cross-circulatory platform to monitor the early recruitment and activation of immune cells in an extracorporeal donor lung by coupling blood perfusion to cell mapping with a fluorescent marker in the pig, a commonly-used species for lung transplantation. The perfusing pig cells were easily detectable in lung cell suspensions, in broncho-alveolar lavages and in different areas of lung sections, indicating infiltration of the organ. Myeloid cells (granulocytes and monocytic cells) were the dominant recruited subsets. Between 6 and 10 h of perfusion, recruited monocytic cells presented a strong upregulation of MHC class II and CD80/86 expression, whereas alveolar macrophages and donor monocytic cells showed no significant modulation of expression. This cross-circulation model allowed us to monitor the initial encounter between perfusing cells and the lung graft, in an easy, rapid, and controllable manner, to generate robust information on innate response and test targeted therapies for improvement of lung transplantation outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Glorion et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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30. Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model.
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De Wolf J, Glorion M, Jouneau L, Estephan J, Leplat JJ, Blanc F, Richard C, Urien C, Roux A, Le Guen M, Journois D, Schwartz-Cornil I, and Sage E
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- Animals, Humans, Lung, Perfusion methods, Renal Dialysis, Swine, Lung Transplantation methods, Organ Preservation methods
- Abstract
Background: Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes., Methods: We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters., Results: Adult and pediatric dialysis stabilized the electrolytic and metabolic profiles while maintaining acid-base and gas exchanges. Pediatric dialysis increased the level of IL-10 and IL-6 in the perfusate. Despite leading to modification of the perfusate composition, the 4 EVLP conditions did not affect the gene expression profiles, which were associated in all cases with increased cell survival, cell proliferation, inflammatory response and cell movement, and with inhibition of bleeding., Conclusions: Management of EVLP perfusate by periodic replacement and continuous dialysis has no significant effect on the lung function nor on the gene expression profiles ex vivo. These results suggest that the accumulation of dialyzable cell products does not significantly alter the lung cell response during EVLP, a finding that may have impact on EVLP management in the clinic., Competing Interests: The authors declare no funding and conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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31. Control of IFN-I responses by the aminopeptidase IRAP in neonatal C57BL/6 alveolar macrophages during RSV infection.
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Drajac C, Laubreton D, Marquant Q, Chottin C, Ferret C, Bouguyon E, Schwartz-Cornil I, Saveanu L, Riffault S, and Descamps D
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- Animals, Animals, Newborn, Disease Models, Animal, Host-Pathogen Interactions immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Respiratory Syncytial Virus Infections virology, Signal Transduction, Toll-Like Receptors metabolism, Virus Replication, Cystinyl Aminopeptidase metabolism, Interferon Type I metabolism, Macrophages, Alveolar immunology, Macrophages, Alveolar metabolism, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus Infections metabolism, Respiratory Syncytial Viruses
- Abstract
Respiratory Syncytial Virus (RSV) is the major cause of lower respiratory tract infection in infants, in whom, the sensing of RSV by innate immune receptors and its regulation are still poorly described. However, the severe bronchiolitis following RSV infection in neonates has been associated with a defect in type I interferons (IFN-I) production, a cytokine produced mainly by alveolar macrophages (AMs) upon RSV infection in adults. In the present study, neonatal C57BL/6 AMs mobilized very weakly the IFN-I pathway upon RSV infection in vitro and failed to restrain virus replication. However, IFN-I productions by neonatal AMs were substantially increased by the deletion of Insulin-Responsive AminoPeptidase (IRAP), a protein previously involved in the regulation of IFN-I production by dendritic cells. Moreover, neonatal IRAP
KO AMs showed a higher expression of IFN-stimulated genes than their wild-type C57BL/6 counterpart. Interestingly, depletion of IRAP did not affect adult AM responses. Finally, we demonstrated that newborn IRAPKO mice infected with RSV had more IFN-I in their lungs and eliminated the virus more efficiently than WT neonates. Taken together, early-life susceptibility to RSV infection may be related to an original age-dependent suppressive function of IRAP on the IFN-I driven-antiviral responses in neonatal AMs.- Published
- 2021
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32. Single-Shot Vaccines against Bovine Respiratory Syncytial Virus (BRSV): Comparative Evaluation of Long-Term Protection after Immunization in the Presence of BRSV-Specific Maternal Antibodies.
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Valarcher JF, Hägglund S, Näslund K, Jouneau L, Malmström E, Boulesteix O, Pinard A, Leguéré D, Deslis A, Gauthier D, Dubuquoy C, Pietralunga V, Rémot A, Falk A, Shevchenko G, Bergström Lind S, Von Brömssen C, Vargmar K, Zhang B, Kwong PD, Rodriguez MJ, Garcia Duran M, Schwartz-Cornil I, Taylor G, and Riffault S
- Abstract
The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and Montanide
TM ISA61 VG (ISA61, n = 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV, n = 6), (iii) a commercial vaccine (CV, n = 6), or were injected with ISA61 alone ( n = 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.- Published
- 2021
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33. A Single Shot Pre-fusion-Stabilized Bovine RSV F Vaccine is Safe and Effective in Newborn Calves with Maternally Derived Antibodies.
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Riffault S, Hägglund S, Guzman E, Näslund K, Jouneau L, Dubuquoy C, Pietralunga V, Laubreton D, Boulesteix O, Gauthier D, Remot A, Boukaridi A, Falk A, Shevchenko G, Lind SB, Vargmar K, Zhang B, Kwong PD, Rodriguez MJ, Duran MG, Schwartz-Cornil I, Eléouët JF, Taylor G, and Valarcher JF
- Abstract
Achieving safe and protective vaccination against respiratory syncytial virus (RSV) in infants and in calves has proven a challenging task. The design of recombinant antigens with a conformation close to their native form in virus particles is a major breakthrough. We compared two subunit vaccines, the bovine RSV (BRSV) pre-fusion F (preF) alone or with nanorings formed by the RSV nucleoprotein (preF+N). PreF and N proteins are potent antigenic targets for neutralizing antibodies and T cell responses, respectively. To tackle the challenges of neonatal immunization, three groups of six one-month-old calves with maternally derived serum antibodies (MDA) to BRSV received a single intramuscular injection of PreF, preF+N with Montanide
TM ISA61 VG (ISA61) as adjuvant or only ISA61 (control). One month later, all calves were challenged with BRSV and monitored for virus replication in the upper respiratory tract and for clinical signs of disease over one week, and then post-mortem examinations of their lungs were performed. Both preF and preF+N vaccines afforded safe, clinical, and virological protection against BRSV, with little difference between the two subunit vaccines. Analysis of immune parameters pointed to neutralizing antibodies and antibodies to preF as being significant correlates of protection. Thus, a single shot vaccination with preF appears sufficient to reduce the burden of BRSV disease in calves with MDA.- Published
- 2020
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34. The antibody response induced FMDV vaccines in sheep correlates with early transcriptomic responses in blood.
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Jouneau L, Lefebvre DJ, Costa F, Romey A, Blaise-Boisseau S, Relmy A, Jaszczyszyn Y, Dard-Dascot C, Déjean S, Versillé N, Guitton E, Hudelet P, Curet M, De Clercq K, Bakkali-Kassimi L, Zientara S, Klonjkowski B, and Schwartz-Cornil I
- Abstract
Foot and mouth disease (FMD) is a highly contagious viral disease with high economic impact, representing a major threat for cloven-hooved mammals worldwide. Vaccines based on adjuvanted inactivated virus (iFMDV) induce effective protective immunity implicating antibody (Ab) responses. To reduce the biosafety constraints of the manufacturing process, a non-replicative human adenovirus type 5 vector encoding FMDV antigens (Ad5-FMDV) has been developed. Here we compared the immunogenicity of iFMDV and Ad5-FMDV with and without the ISA206VG emulsion-type adjuvant in sheep. Contrasted Ab responses were obtained: iFMDV induced the highest Ab levels, Ad5-FMDV the lowest ones, and ISA206VG increased the Ad5-FMDV-induced Ab responses to protective levels. Each vaccine generated heterogeneous Ab responses, with high and low responders, the latter being considered as obstacles to vaccine effectiveness. A transcriptomic study on total blood responses at 24 h post-vaccination revealed several blood gene module activities correlating with long-term Ab responses. Downmodulation of T cell modules' activities correlated with high responses to iFMDV and to Ad5-FMDV+ISA206VG vaccines as also found in other systems vaccinology studies in humans and sheep. The impact of cell cycle activity depended on the vaccine types, as it positively correlated with higher responses to iFMDV but negatively to non-adjuvanted Ad5-FMDV. Finally an elevated B cell activity at 24 h correlated with high Ab responses to the Ad5-FMDV+ISA206VG vaccine. This study provides insights into the early mechanisms driving the Ab response induced by different vaccine regimens including Ad5 vectors and points to T cell modules as early biomarker candidates of different vaccine-type efficacy across species., Competing Interests: Competing interestsN.V. is employed by SEPPIC. P.H. and M.C. are employed by Merial-Boehringer Ingelheim. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The other authors declare no competing interest., (© The Author(s) 2020.)
- Published
- 2020
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35. Electroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigs.
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Bernelin-Cottet C, Urien C, McCaffrey J, Collins D, Donadei A, McDaid D, Jakob V, Barnier-Quer C, Collin N, Bouguyon E, Bordet E, Barc C, Boulesteix O, Leplat JJ, Blanc F, Contreras V, Bertho N, Moore AC, and Schwartz-Cornil I
- Subjects
- Animals, Female, Immunity, Cellular immunology, Immunity, Humoral immunology, Inflammation etiology, Male, Needles, Plasmids, Species Specificity, Swine, Vaccines, DNA immunology, Vaccines, DNA toxicity, Electroporation methods, Nanoparticles, Vaccination methods, Vaccines, DNA administration & dosage
- Abstract
DNA vaccination is an attractive technology, based on its well-established manufacturing process, safety profile, adaptability to rapidly combat pandemic pathogens, and stability at ambient temperature; however an optimal delivery method of DNA remains to be determined. As pigs are a relevant model for humans, we comparatively evaluated the efficiency of vaccine DNA delivery in vivo to pigs using dissolvable microneedle patches, intradermal inoculation with needle (ID), surface electroporation (EP), with DNA associated or not to cationic poly-lactic-co-glycolic acid nanoparticles (NPs). We used a luciferase encoding plasmid (pLuc) as a reporter and vaccine plasmids encoding antigens from the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a clinically-significant swine arterivirus. Patches were successful at inducing luciferase expression in skin although at lower level than EP. EP induced the cutaneaous recruitment of granulocytes, of MHC2
pos CD172Apos myeloid cells and type 1 conventional dendritic cells, in association with local production of IL-1β, IL-8 and IL-17; these local responses were more limited with ID and undetectable with patches. The addition of NP to EP especially promoted the recruitment of the MHC2pos CD172Apos CD163int and CD163neg myeloid subsets. Notably we obtained the strongest and broadest IFNγ T-cell response against a panel of PRRSV antigens with DNA + NPs delivered by EP, whereas patches and ID were ineffective. The anti-PRRSV IgG responses were the highest with EP administration independently of NPs, mild with ID, and undetectable with patches. These results contrast with the immunogenicity and efficacy previously induced in mice with patches. This study concludes that successful DNA vaccine administration in skin can be achieved in pigs with electroporation and patches, but only the former induces local inflammation, humoral and cellular immunity, with the highest potency when NPs were used. This finding shows the importance of evaluating the delivery and immunogenicity of DNA vaccines beyond the mouse model in a preclinical model relevant to human such as pig and reveals that EP with DNA combined to NP induces strong immunogenicity., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2019
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36. A DNA Prime Immuno-Potentiates a Modified Live Vaccine against the Porcine Reproductive and Respiratory Syndrome Virus but Does Not Improve Heterologous Protection.
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Bernelin-Cottet C, Urien C, Fretaud M, Langevin C, Trus I, Jouneau L, Blanc F, Leplat JJ, Barc C, Boulesteix O, Riou M, Dysart M, Mahé S, Studsrub E, Nauwynck H, Bertho N, Bourry O, and Schwartz-Cornil I
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Immunologic Factors metabolism, Interferon-gamma metabolism, Nasal Mucosa virology, Porcine respiratory and reproductive syndrome virus genetics, Swine, T-Lymphocytes immunology, Treatment Outcome, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Vaccines, DNA administration & dosage, Viral Load, Viral Vaccines administration & dosage, Virus Shedding, Immunity, Heterologous, Immunization Schedule, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine respiratory and reproductive syndrome virus immunology, Vaccines, DNA immunology, Viral Vaccines immunology
- Abstract
The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus inducing abortion in sows and respiratory disease in young pigs, is a leading infectious cause of economic losses in the swine industry. Modified live vaccines (MLVs) help in controlling the disease, but their efficacy is often compromised by the high genetic diversity of circulating viruses, leading to vaccine escape variants in the field. In this study, we hypothesized that a DNA prime with naked plasmids encoding PRRSV antigens containing conserved T-cell epitopes may improve the protection of MLV against a heterologous challenge. Plasmids were delivered with surface electroporation or needle-free jet injection and European strain-derived PRRSV antigens were targeted or not to the dendritic cell receptor XCR1. Compared to MLV-alone, the DNA-MLV prime- boost regimen slightly improved the IFNγ T-cell response, and substantially increased the antibody response against envelope motives and the nucleoprotein N. The XCR1-targeting of N significantly improved the anti-N specific antibody response. Despite this immuno-potentiation, the DNA-MLV regimen did not further decrease the serum viral load or the nasal viral shedding of the challenge strain over MLV-alone. Finally, the heterologous protection, achieved in absence of detectable effective neutralizing antibodies, was not correlated to the measured antibody or to the IFNγ T-cell response. Therefore, immune correlates of protection remain to be identified and represent an important gap of knowledge in PRRSV vaccinology. This study importantly shows that a naked DNA prime immuno-potentiates an MLV, more on the B than on the IFNγ T-cell response side, and has to be further improved to reach cross-protection.
- Published
- 2019
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37. A DNA-Modified Live Vaccine Prime-Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus.
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Bernelin-Cottet C, Urien C, Stubsrud E, Jakob V, Bouguyon E, Bordet E, Barc C, Boulesteix O, Contreras V, Barnier-Quer C, Collin N, Trus I, Nauwynck H, Bertho N, and Schwartz-Cornil I
- Subjects
- Animals, Antibody Formation, Immunity, Cellular, Organisms, Genetically Modified genetics, Organisms, Genetically Modified immunology, Porcine respiratory and reproductive syndrome virus genetics, Swine, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated genetics, Vaccines, Attenuated immunology, Vaccines, DNA administration & dosage, Vaccines, DNA genetics, Viral Vaccines administration & dosage, Viral Vaccines genetics, Antibodies, Viral blood, Immunization Schedule, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine respiratory and reproductive syndrome virus immunology, T-Lymphocytes immunology, Vaccines, DNA immunology, Viral Vaccines immunology
- Abstract
The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection against heterologous viral variants. With the goal to induce broad and cross-protective immunity, we generated DNA vaccines encoding B and T antigens derived from a European subtype 1 strain that include T-cell epitope sequences known to be conserved across strains. These antigens were expressed either in a native form or in the form of vaccibodies targeted to the endocytic receptor XCR1 and CD11c expressed by different types of antigen-presenting cells (APCs). When delivered in skin with cationic nanoparticles and surface electroporation, multiple DNA vaccinations as a stand-alone regimen induced substantial antibody and T-cell responses, which were not promoted by targeting antigens to APCs. Interestingly, a DNA-MLV prime-boost strategy strongly enhanced the antibody response and broadened the T-cell responses over the one induced by MLV or DNA-only. The anti-nucleoprotein antibody response induced by the DNA-MLV prime-boost was clearly promoted by targeting the antigen to CD11c and XCR1, indicating a benefit of APC-targeting on the B-cell response. In conclusion, a DNA-MLV prime-boost strategy, by enhancing the potency and breadth of MLV vaccines, stands as a promising vaccine strategy to improve the control of PRRSV in infected herds.
- Published
- 2019
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38. Macrophage-B Cell Interactions in the Inverted Porcine Lymph Node and Their Response to Porcine Reproductive and Respiratory Syndrome Virus.
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Bordet E, Frétaud M, Crisci E, Bouguyon E, Rault S, Pezant J, Pleau A, Renson P, Giuffra E, Larcher T, Bourge M, Bourry O, Boulesteix O, Langevin C, Schwartz-Cornil I, and Bertho N
- Subjects
- Animals, Porcine respiratory and reproductive syndrome virus, Swine, B-Lymphocytes immunology, Lymph Nodes immunology, Macrophages immunology, Porcine Reproductive and Respiratory Syndrome immunology
- Abstract
Swine lymph nodes (LN) present an inverted structure compared to mouse and human, with the afferent lymph diffusing from the center to the periphery. This structure, also observed in close and distant species such as dolphins, hippopotamus, rhinoceros, and elephants, is poorly described, nor are the LN macrophage populations and their relationship with B cell follicles. B cell maturation occurs mainly in LN B cell follicles with the help of LN macrophage populations endowed with different antigen delivery capacities. We identified three macrophage populations that we localized in the inverted LN spatial organization. This allowed us to ascribe porcine LN MΦ to their murine counterparts: subcapsular sinus MΦ, medullary cord MΦ and medullary sinus MΦ. We identified the different intra and extrafollicular stages of LN B cells maturation and explored the interaction of MΦ, drained antigen and follicular B cells. The porcine reproductive and respiratory syndrome virus (PRRSV) is a major porcine pathogen that infects tissue macrophages (MΦ). PRRSV is persistent in the secondary lymphoid tissues and induces a delay in neutralizing antibodies appearance. We observed PRRSV interaction with two LN MΦ populations, of which one interacts closely with centroblasts. We observed BCL6 up-regulation in centroblast upon PRRSV infection, leading to new hypothesis on PRRSV inhibition of B cell maturation. This seminal study of porcine LN will permit fruitful comparison with murine and human LN for a better understanding of normal and inverted LN development and functioning.
- Published
- 2019
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39. A DNA Vaccine Encoding the Gn Ectodomain of Rift Valley Fever Virus Protects Mice via a Humoral Response Decreased by DEC205 Targeting.
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Chrun T, Lacôte S, Urien C, Richard CA, Tenbusch M, Aubrey N, Pulido C, Lakhdar L, Marianneau P, and Schwartz-Cornil I
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- Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antibody Formation immunology, CHO Cells, Cell Line, Cricetulus, HEK293 Cells, Humans, Mice, Mice, Inbred BALB C, Viral Envelope Proteins immunology, Glycoproteins immunology, Immunity, Humoral immunology, Rift Valley fever virus immunology, Vaccines, DNA immunology, Viral Vaccines immunology
- Abstract
The Rift Valley fever virus (RVFV) is responsible for a serious mosquito-borne viral disease in humans and ruminants. The development of a new and safer vaccine is urgently needed due to the risk of introduction of this arbovirus into RVFV-free continents. We recently showed that a DNA vaccine encoding eGn, the ectodomain of the RVFV Gn glycoprotein, conferred a substantial protection in the sheep natural host and that the anti-eGn IgG levels correlated to protection. Addressing eGn to DEC205 reduced the protective efficacy while decreasing the antibody and increasing the IFNγ T cell responses in sheep. In order to get further insight into the involved mechanisms, we evaluated our eGn-encoding DNA vaccine strategy in the reference mouse species. A DNA vaccine encoding eGn induced full clinical protection in mice and the passive transfer of immune serum was protective. This further supports that antibodies, although non-neutralizing in vitro , are instrumental in the protection against RVFV. Addressing eGn to DEC205 was also detrimental to protection in mice, and in this species, both the antibody and the IFNγ T cell responses were strongly decreased. Conversely when using a plasmid encoding a different antigen, i.e., mCherry, DEC205 targeting promoted the antibody response. Altogether our results show that the outcome of targeting antigens to DEC205 depends on the species and on the fused antigen and is not favorable in the case of eGn. In addition, we bring evidences that eGn in itself is a pertinent antigen to be included in a DNA vaccine and that next developments should aim at promoting the anti-eGn antibody response.
- Published
- 2019
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40. Porcine Reproductive and Respiratory Syndrome Virus Type 1.3 Lena Triggers Conventional Dendritic Cells 1 Activation and T Helper 1 Immune Response Without Infecting Dendritic Cells.
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Bordet E, Blanc F, Tiret M, Crisci E, Bouguyon E, Renson P, Maisonnasse P, Bourge M, Leplat JJ, Giuffra E, Jouneau L, Schwartz-Cornil I, Bourry O, and Bertho N
- Subjects
- Animals, Biomarkers, Cytokines metabolism, Dendritic Cells metabolism, Lymphocyte Activation immunology, Lymphocyte Culture Test, Mixed, Porcine Reproductive and Respiratory Syndrome metabolism, Swine, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Helper-Inducer metabolism, Dendritic Cells immunology, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is an arterivirus responsible for highly contagious infection and huge economic losses in pig industry. Two species, PRRSV-1 and PRRSV-2 are distinguished, PRRSV-1 being more prevalent in Europe. PRRSV-1 can further be divided in subtypes. PRRSV-1.3 such as Lena are more pathogenic than PRRSV-1.1 such as Lelystad or Flanders13. PRRSV-1.3 viruses trigger a higher Th1 response than PRRSV-1.1, although the role of the cellular immune response in PRRSV clearance remains ill defined. The pathogenicity as well as the T cell response inductions may be differentially impacted according to the capacity of the virus strain to infect and/or activate DCs. However, the interactions of PRRSV with in vivo -differentiated-DC subtypes such as conventional DC1 (cDC1), cDC2, and monocyte-derived DCs (moDC) have not been thoroughly investigated. Here, DC subpopulations from Lena in vivo infected pigs were analyzed for viral genome detection. This experiment demonstrates that cDC1, cDC2, and moDC are not infected in vivo by Lena. Analysis of DC cytokines production revealed that cDC1 are clearly activated in vivo by Lena. In vitro comparison of 3 Europeans strains revealed no infection of the cDC1 and cDC2 and no or little infection of moDC with Lena, whereas the two PRRSV-1.1 strains infect none of the 3 DC subtypes. In vitro investigation of T helper polarization and cytokines production demonstrate that Lena induces a higher Th1 polarization and IFNγ secretion than FL13 and LV. Altogether, this work suggests an activation of cDC1 by Lena associated with a Th1 immune response polarization.
- Published
- 2018
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41. Porcine Alveolar Macrophage-like cells are pro-inflammatory Pulmonary Intravascular Macrophages that produce large titers of Porcine Reproductive and Respiratory Syndrome Virus.
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Bordet E, Maisonnasse P, Renson P, Bouguyon E, Crisci E, Tiret M, Descamps D, Bernelin-Cottet C, Urien C, Lefèvre F, Jouneau L, Bourry O, Leplat JJ, Schwartz-Cornil I, and Bertho N
- Subjects
- Animals, Cells, Cultured, Female, Lung cytology, Lung immunology, Lung virology, Macrophages, Alveolar virology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus pathogenicity, Primary Cell Culture, Specific Pathogen-Free Organisms, Sus scrofa, Swine, Swine, Miniature, Viremia virology, Macrophages, Alveolar immunology, Phagocytosis, Porcine Reproductive and Respiratory Syndrome immunology, Porcine respiratory and reproductive syndrome virus immunology, Viremia immunology
- Abstract
Lung inflammation is frequently involved in respiratory conditions and it is strongly controlled by mononuclear phagocytes (MNP). We previously studied porcine lung MNP and described a new population of cells presenting all the features of alveolar macrophages (AM) except for their parenchymal location, that we named AM-like cells. Herein we showed that AM-like cells are macrophages phagocytosing blood-borne particles, in agreement with a pulmonary intravascular macrophages (PIM) identity. PIM have been described microscopically long time ago in species from the Laurasiatheria superorder such as bovine, swine, cats or cetaceans. We observed that PIM were more inflammatory than AM upon infection with the porcine reproductive and respiratory syndrome virus (PRRSV), a major swine pathogen. Moreover, whereas PRRSV was thought to mainly target AM, we observed that PIM were a major producer of virus. The PIM infection was more correlated with viremia in vivo than AM infection. Finally like AM, PIM-expressed genes were characteristic of an embryonic monocyte-derived macrophage population, whose turnover is independent of bone marrow-derived hematopoietic precursors. This last observation raised the interesting possibility that AM and PIM originate from the same lung precursor.
- Published
- 2018
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42. A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting.
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Chrun T, Lacôte S, Urien C, Jouneau L, Barc C, Bouguyon E, Contreras V, Ferrier-Rembert A, Peyrefitte CN, Busquets N, Vidal E, Pujols J, Marianneau P, and Schwartz-Cornil I
- Abstract
Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available outside areas of endemicity. In this study, we evaluated in sheep the protective immunity induced by DNA vaccines encoding the extracellular portion of the Gn antigen which was either or not targeted to antigen-presenting cells. The DNA encoding untargeted antigen was the most potent at inducing IgG responses, although not neutralizing, and conferred a significant clinical and virological protection upon infectious challenge, superior to DNA vaccines encoding the targeted antigen. A statistical analysis of the challenge parameters supported that the anti-eGn IgG, rather than the T-cell response, was instrumental in protection. Altogether, this work shows that a DNA vaccine encoding the extracellular portion of the Gn antigen confers substantial- although incomplete -protective immunity in sheep, a natural host with high preclinical relevance, and provides some insights into key immune correlates useful for further vaccine improvements against the Rift Valley fever virus., Competing Interests: The authors declare no competing interests.
- Published
- 2018
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43. The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin.
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Deloizy C, Fossum E, Barnier-Quer C, Urien C, Chrun T, Duval A, Codjovi M, Bouguyon E, Maisonnasse P, Hervé PL, Barc C, Boulesteix O, Pezant J, Chevalier C, Collin N, Dalod M, Bogen B, Bertho N, and Schwartz-Cornil I
- Subjects
- Adjuvants, Immunologic administration & dosage, Animals, Antibodies, Viral blood, Chemokines, C administration & dosage, Chemokines, C genetics, Dendritic Cells metabolism, Immunoglobulin G blood, Influenza Vaccines administration & dosage, Influenza Vaccines genetics, Influenza Vaccines immunology, Oligodeoxyribonucleotides administration & dosage, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins genetics, Skin metabolism, Swine, Viral Matrix Proteins administration & dosage, Viral Matrix Proteins genetics, Antibody Formation, Chemokines, C metabolism, Dendritic Cells immunology, Receptors, G-Protein-Coupled metabolism, Recombinant Fusion Proteins immunology, Skin immunology, Viral Matrix Proteins immunology
- Abstract
XCR1 is selectively expressed on a conventional dendritic cell subset, the cDC1 subset, through phylogenetically distant species. The outcome of antigen-targeting to XCR1 may therefore be similar across species, permitting the translation of results from experimental models to human and veterinary applications. Here we evaluated in pigs the immunogenicity of bivalent protein structures made of XCL1 fused to the external portion of the influenza virus M2 proton pump, which is conserved through strains and a candidate for universal influenza vaccines. Pigs represent a relevant target of such universal vaccines as pigs can be infected by swine, human and avian strains. We found that cDC1 were the only cell type labeled by XCR1-targeted mCherry upon intradermal injection in pig skin. XCR1-targeted M2e induced higher IgG responses in seronegative and seropositive pigs as compared to non-targeted M2e. The IgG response was less significantly enhanced by CpG than by XCR1 targeting, and CpG did not further increase the response elicited by XCR1 targeting. Monophosphoryl lipid A with neutral liposomes did not have significant effect. Thus altogether M2e-targeting to XCR1 shows promises for a trans-species universal influenza vaccine strategy, possibly avoiding the use of classical adjuvants.
- Published
- 2017
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44. Corrigendum: A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies.
- Author
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Bernelin-Cottet C, Deloizy C, Stanek O, Barc C, Bouguyon E, Urien C, Boulesteix O, Pezant J, Richard CA, Moudjou M, Costa BD, Jouneau L, Chevalier C, Leclerc C, Sebo P, Bertho N, and Schwartz-Cornil I
- Abstract
[This corrects the article on p. 641 in vol. 7, PMID: 28082980.].
- Published
- 2017
- Full Text
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45. A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies.
- Author
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Bernelin-Cottet C, Deloizy C, Stanek O, Barc C, Bouguyon E, Urien C, Boulesteix O, Pezant J, Richard CA, Moudjou M, Da Costa B, Jouneau L, Chevalier C, Leclerc C, Sebo P, Bertho N, and Schwartz-Cornil I
- Abstract
The development of influenza A virus (IAV) vaccines, which elicits cross-strain immunity against seasonal and pandemic viruses is a major public health goal. As pigs are susceptible to human, avian, and swine-adapted IAV, they would be key targets of so called universal IAV vaccines, for reducing both the zoonotic risk and the economic burden in the swine industry. They also are relevant preclinical models. However, vaccination with conserved IAV antigens (AGs) in pigs was reported to elicit disease exacerbation. In this study, we assessed whether delivery strategies, i.e., dendritic cell (DC) targeting by the intradermal (ID) or intramuscular (IM) routes, impact on the outcome of the vaccination with three conserved IAV AGs (M2e, NP, and HA2) in pigs. The AGs were addressed to CD11c by non-covalent binding to biotinylated anti-CD11c monoclonal antibody. The CD11c-targeted AGs given by the ID route exacerbated disease. Conversely, CD11c-targeted NP injected by the IM route promoted T cell response compared to non-targeted NP. Furthermore, the conserved IAV AGs injected by the IM route, independently of DC targeting, induced both a reduction of viral shedding and a broader IgG response as compared to the ID route. Our findings highlight in a relevant animal species that the route of vaccine delivery impacts on the protection induced by conserved IAV AGs and on vaccine adverse effects. Finally, our results indicate that HA2 stands as the most promising conserved IAV AG for universal vaccine development.
- Published
- 2016
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46. Expanding the tools for identifying mononuclear phagocyte subsets in swine: Reagents to porcine CD11c and XCR1.
- Author
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Deloizy C, Bouguyon E, Fossum E, Sebo P, Osicka R, Bole A, Pierres M, Biacchesi S, Dalod M, Bogen B, Bertho N, and Schwartz-Cornil I
- Subjects
- Animals, Antibodies, Monoclonal metabolism, CD11c Antigen immunology, Cloning, Molecular, Disease Models, Animal, Humans, Immunologic Tests methods, Receptors, G-Protein-Coupled immunology, Veterinary Medicine, CD11c Antigen metabolism, Dendritic Cells physiology, Mononuclear Phagocyte System, Phagocytes immunology, Receptors, G-Protein-Coupled metabolism, Skin metabolism, Swine immunology
- Abstract
Pig is a domestic species of major importance in the agro-economy and in biomedical research. Mononuclear phagocytes (MNP) are organized in subsets with specialized roles in the orchestration of the immune response and new tools are awaited to improve MNP subset identification in the pig. We cloned pig CD11c cDNA and generated a monoclonal antibody to pig CD11c which showed a pattern of expression by blood and skin MNP subsets similar to humans. We also developed a porcine XCL1-mCherry dimer which specifically reacted with the XCR1-expressing dendritic cell subset of the type 1 lineage in blood and skin. These original reagents will allow the efficient identification of pig MNP subsets to study their role in physiological and pathological processes and also to target these cells in novel intervention and vaccine strategies for veterinary applications and preclinical evaluations., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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47. bFGF Up-regulation Reduces Spontaneous Necrosis of VX2 Tumors Without Increasing Tumoral Microvascular Density.
- Author
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Pascale F, Ghegediban SH, Bedouet L, Namur J, Bonneau M, Verret V, Schwartz-Cornil I, Wassef M, and Laurent A
- Subjects
- Animals, Cell Line, Tumor, Microvessels pathology, Necrosis, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic pathology, Rabbits, Up-Regulation, Fibroblast Growth Factor 2 metabolism, Liver Neoplasms, Experimental blood supply, Liver Neoplasms, Experimental metabolism
- Abstract
Aim: To determine whether up-regulation of basic fibroblast growth factor (bFGF) in VX2 cells reduces tumor necrosis., Materials and Methods: VX2 cells were transfected with expression vector containing cDNA of rabbit bFGF. Stable clones producing rabbit bFGF (bFGF-VX2) were selected. bFGF-VX2 (n=5) or non-transfected VX2 (control) (n=5) cells were implanted into leg muscle of 10 rabbits. The tumors were characterized 21 days after grafting., Results: Overexpression of bFGF by VX2 tumors significantly reduced necrosis (p<0.0223) and increased cell viability (p<0.0223), without effect on the mean vascular density. bFGF concentration was significantly higher in bFGF-VX2 tumors (p<0.0062) and negatively correlated with tumor volume at day 21 (ρ=-0.927, p<0.0034). Vascular endothelial growth factor concentration was significantly lower in bFGF-VX2 tumors (p<0.0105) and negatively correlated with the bFGF concentration of tumors (ρ=-0.903, p<0.0067)., Conclusion: The overexpression of bFGF in VX2 cells increased tumor viability and reduced necrosis, making the evaluation of long-term anticancer therapies possible in this model., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2016
48. Induction and control of the type I interferon pathway by Bluetongue virus.
- Author
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Vitour D, Doceul V, Schwartz-Cornil I, and Zientara S
- Abstract
Upon viral infection, infected cells mount an antiviral response that culminates with the production of type I IFN (IFN-α/β) and other pro-inflammatory cytokines that control the infection. Production of type I IFN occurs both in vivo and in vitro in response to Bluetongue virus (BTV), an arthropod-borne virus, but the underlying mechanisms responsible for this event remained unknown until recently. This review describes the recent advances in the identification of cellular sensors and signalling pathways involved in this process. In non-hematopoietic cells, expression of IFN-β in response to BTV infection depends on the activation of the RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). In contrast, induction of IFN-α/β synthesis in sheep primary plasmacytoid dendritic cells (pDCs) required the MyD88 adaptor independently of the Toll-like receptor 7 (TLR7), as well as the kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK). In order to counteract this antiviral response, most of viruses have elaborated mechanisms to hinder its action. This review also describes the ability of BTV to interfere with the IFN pathway and the recent findings describing the non-structural viral protein NS3 as a powerful antagonist of the host cellular response.
- Published
- 2015
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49. Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics.
- Author
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Vu Manh TP, Elhmouzi-Younes J, Urien C, Ruscanu S, Jouneau L, Bourge M, Moroldo M, Foucras G, Salmon H, Marty H, Quéré P, Bertho N, Boudinot P, Dalod M, and Schwartz-Cornil I
- Abstract
Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover, we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey.
- Published
- 2015
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50. Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions.
- Author
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Vu Manh TP, Bertho N, Hosmalin A, Schwartz-Cornil I, and Dalod M
- Abstract
Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and species.
- Published
- 2015
- Full Text
- View/download PDF
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