Author: "Céline Barc" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Céline Barc"' showing total 59 results

Start Over Author "Céline Barc"

59 results on '"Céline Barc"'

1. Characterization of intestinal mononuclear phagocyte subsets in young ruminants at homeostasis and during Cryptosporidium parvum infection

Author: Ambre Baillou, Florian Tomal, Thierry Chaumeil, Céline Barc, Yves Levern, Alix Sausset, Tiffany Pezier, Julie Schulthess, Pauline Peltier-Pain, Fabrice Laurent, and Sonia Lacroix-Lamandé
Subjects: mononuclear phagocytes, dendritic cells, ruminants, intestine, Cryptosporidium parvum, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionCryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, Cryptosporidium parvum, with a high prevalence in livestock (cattle, sheep, and goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and particularly of type 1 conventional dendritic cells (cDC1) among mononuclear phagocytes (MPs) in controlling the acute phase of C. parvum infection. These immune populations are well described in mice and humans, but their fine characterization in the intestine of young ruminants remained to be further explored.MethodsImmune cells of the small intestinal Peyer’s patches and of the distal jejunum were isolated from naive lambs and calves at different ages. This was followed by their fine characterization by flow cytometry and transcriptomic analyses (q-RT-PCR and single cell RNAseq (lamb cells)). Newborn animals were infected with C. parvum, clinical signs and parasite burden were quantified, and isolated MP cells were characterized by flow cytometry in comparison with age matched control animals.ResultsHere, we identified one population of macrophages and three subsets of cDC (cDC1, cDC2, and a minor cDC subset with migratory properties) in the intestine of lamb and calf by phenotypic and targeted gene expression analyses. Unsupervised single-cell transcriptomic analysis confirmed the identification of these four intestinal MP subpopulations in lamb, while highlighting a deeper diversity of cell subsets among monocytic and dendritic cells. We demonstrated a weak proportion of cDC1 in the intestine of highly susceptible newborn lambs together with an increase of these cells within the first days of life and in response to the infection.DiscussionConsidering cDC1 importance for efficient parasite control in the mouse model, one may speculate that the cDC1/cDC2 ratio plays also a key role for the efficient control of C. parvum in young ruminants. In this study, we established the first fine characterization of intestinal MP subsets in young lambs and calves providing new insights for comparative immunology of the intestinal MP system across species and for future investigations on host–Cryptosporidium interactions in target species.
Published: 2024
Full Text: View/download PDF

2. Tetrafunctional Block Copolymers Promote Lung Gene Transfer in Newborn Piglets

Author: Ignacio Caballero, Mickaël Riou, Océane Hacquin, Claire Chevaleyre, Céline Barc, Jérémy Pezant, Anne Pinard, Julien Fassy, Roger Rezzonico, Bernard Mari, Nathalie Heuzé-Vourc’h, Bruno Pitard, and Georges Vassaux
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Tetrafunctional block copolymers are molecules capable of complexing DNA. Although ineffective in vitro, studies in mice have shown that the tetrafunctional block copolymer 704 is a more efficient lung gene transfer agent than the cationic liposome GL67A, previously used in a phase II clinical trial in cystic fibrosis patients. In the present study, we compared the gene transfer capacity of the 704-DNA formulation and a cationic liposome-DNA formulation equivalent to GL67A in a larger-animal model, the newborn piglet. Our results indicate an efficacy of the 704-DNA formulation well above one order of magnitude higher than that of the cationic liposome-DNA formulation, with no elevated levels of interleukin-6 (IL-6), taken as a marker of inflammation. Transgene expression was heterogeneous within lung lobes, with expression levels that were below the detection threshold in some samples, while high in other samples. This heterogeneity is likely to be due to the bolus injection procedure as well as to the small volume of injection. The present study highlights the potential of tetrafunctional block copolymers as non-viral vectors for lung gene therapy. Keywords: tetrafunctional block copolymers, lungs, gene therapy, non-viral vector, newborn pigs
Published: 2019
Full Text: View/download PDF

3. The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin

Author: Charlotte Deloizy, Even Fossum, Christophe Barnier-Quer, Céline Urien, Tiphany Chrun, Audrey Duval, Maelle Codjovi, Edwige Bouguyon, Pauline Maisonnasse, Pierre-Louis Hervé, Céline Barc, Olivier Boulesteix, Jérémy Pezant, Christophe Chevalier, Nicolas Collin, Marc Dalod, Bjarne Bogen, Nicolas Bertho, and Isabelle Schwartz-Cornil
Subjects: Medicine, Science
Abstract: 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
Full Text: View/download PDF

4. Local immunization impacts the response of dairy cows to Escherichia coli mastitis

Author: Vincent Herry, Christophe Gitton, Guillaume Tabouret, Maryline Répérant, Laurine Forge, Christian Tasca, Florence B. Gilbert, Edouard Guitton, Céline Barc, Christophe Staub, David G. E. Smith, Pierre Germon, Gilles Foucras, and Pascal Rainard
Subjects: Medicine, Science
Abstract: Abstract Current vaccines to Escherichia coli mastitis have shown some albeit limited efficacy. Their mode of action has not been documented, and immune responses protecting the mammary gland against E. coli are not completely understood. To improve our knowledge of mammary gland immune protection, cows immunized either intramuscularly or intramammarily with the E. coli P4 were submitted to a homologous mastitis challenge. A third group of mock-immunized cows serve as challenge controls. Local immunization modified favorably the course of infection, by improving bacterial clearance while limiting inflammation. Systemic clinical signs and reduction in milk secretion were also contained. This occurred with a modification of the cytokine profile, such as an increase in IFN-γ and a reduction in TNF-α concentrations in milk. Concentrations of IL-17A and IL-22 increased in milk at the onset of the inflammatory response and remained high up to the elimination of bacteria, but concentrations did not differ between groups. Accelerated bacteriological cure was not linked to an increase in the initial efficiency of phagocytosis in milk. Results support the idea that antibodies did not play a major role in the improvement, and that cell-mediated immunity is the key to understanding E. coli vaccine-induced protection of the mammary gland.
Published: 2017
Full Text: View/download PDF

5. Establishment of a Newborn Lamb Gut-Loop Model to Evaluate New Methods of Enteric Disease Control and Reduce Experimental Animal Use

Author: Ambre Baillou, Nathalie Kasal-Hoc, Céline Barc, Juliette Cognié, Anne Pinard, Jérémy Pezant, Julie Schulthess, Pauline Peltier-Pain, Sonia Lacroix-Lamandé, and Fabrice Laurent
Subjects: newborn lamb, multiple intestinal loop model, 3R, Cryptosporidium parvum, yeast cell wall fractions, Veterinary medicine, SF600-1100
Abstract: Enteric infectious diseases are not all well controlled, which leads to animal suffering and sometimes death in the most severe cases, in addition to economic losses for farmers. Typical symptoms of enteric infections include watery diarrhea, stomach cramps or pain, dehydration, nausea, vomiting, fever and weight loss. Evaluation of new control methods against enteric infections requires the use of many animals. We aimed to develop a new method for an initial in vivo screen of promising compounds against neonatal diseases such as cryptosporidiosis while limiting experimental animal use. We therefore adapted an in vivo method of multiple consecutive but independent intestinal loops to newborn lambs delivered by cesarean section, in which endotoxin responsiveness is retained. This new method allowed for the screening of natural yeast fractions for their ability to stimulate immune responses and to limit early Cryptosporidium parvum development. This model may also be used to investigate host–pathogen interactions and immune responses in a neonatal controlled environment.
Published: 2021
Full Text: View/download PDF

6. Corrigendum: A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

Author: Cindy Bernelin-Cottet, Charlotte Deloizy, Ondrej Stanek, Céline Barc, Edwige Bouguyon, Céline Urien, Olivier Boulesteix, Jérémy Pezant, Charles-Adrien Richard, Mohammed Moudjou, Bruno Da Costa, Luc Jouneau, Christophe Chevalier, Claude Leclerc, Peter Sebo, Nicolas Bertho, and Isabelle Schwartz-Cornil
Subjects: dendritic cells, swine, human, vaccines, routes of administration, Immunologic diseases. Allergy, RC581-607
Published: 2017
Full Text: View/download PDF

7. A DNA Prime Immuno-Potentiates a Modified Live Vaccine against the Porcine Reproductive and Respiratory Syndrome Virus but Does Not Improve Heterologous Protection

Author: Cindy Bernelin-Cottet, Céline Urien, Maxence Fretaud, Christelle Langevin, Ivan Trus, Luc Jouneau, Fany Blanc, Jean-Jacques Leplat, Céline Barc, Olivier Boulesteix, Mickaël Riou, Marilyn Dysart, Sophie Mahé, Elisabeth Studsrub, Hans Nauwynck, Nicolas Bertho, Olivier Bourry, and Isabelle Schwartz-Cornil
Subjects: PRRSV, DNA vaccine, modified-live vaccine, antigen-presenting cell targeting, pigs, Microbiology, QR1-502
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
Full Text: View/download PDF

8. 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

Author: Cindy Bernelin-Cottet, Céline Urien, Elisabeth Stubsrud, Virginie Jakob, Edwige Bouguyon, Elise Bordet, Céline Barc, Olivier Boulesteix, Vanessa Contreras, Christophe Barnier-Quer, Nicolas Collin, Ivan Trus, Hans Nauwynck, Nicolas Bertho, and Isabelle Schwartz-Cornil
Subjects: PRRSV, DNA vaccine, modified-live vaccine, antigen-presenting cell targeting, pigs, Microbiology, QR1-502
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
Full Text: View/download PDF

9. The Pig: A Relevant Model for Evaluating the Neutrophil Serine Protease Activities during Acute Pseudomonas aeruginosa Lung Infection.

Author: Claire Chevaleyre, Mickaël Riou, Déborah Bréa, Clarisse Vandebrouck, Céline Barc, Jérémy Pezant, Sandrine Melo, Michel Olivier, Rémy Delaunay, Olivier Boulesteix, Patricia Berthon, Christelle Rossignol, Julien Burlaud Gaillard, Frédéric Becq, Francis Gauthier, Mustapha Si-Tahar, François Meurens, Mustapha Berri, Ignacio Caballero-Posadas, and Sylvie Attucci
Subjects: Medicine, Science
Abstract: The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues. We induced acute neutrophilic inflammatory responses in pig lungs using Pseudomonas aeruginosa, an opportunistic respiratory pathogen. Blood samples, nasal swabs and bronchoalveolar lavage fluids (BALFs) were collected at 0, 3, 6 and 24 h post-insfection (p.i.) and biochemical parameters, serum and BAL cytokines, bacterial cultures and neutrophil activity were evaluated. The release of proinflammatory mediators, biochemical and hematological blood parameters, cell recruitment and bronchial reactivity, peaked at 6h p.i.. We also used synthetic substrates specific for human neutrophil proteases to show that the activity of pig NSPs in BALFs increased. These proteases were also detected at the surface of lung neutrophils using anti-human NSP antibodies. Pseudomonas aeruginosa-induced lung infection in pigs results in a neutrophilic response similar to that described for cystic fibrosis and ventilator-associated pneumonia in humans. Altogether, this indicates that the pig is an appropriate model for testing anti-infectious and/or anti-inflammatory drugs to combat adverse proteolytic effects of neutrophil in human lung diseases.
Published: 2016
Full Text: View/download PDF

10. Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.

Author: Pierre Sarradin, Céline Viglietta, Claude Limouzin, Olivier Andréoletti, Nathalie Daniel-Carlier, Céline Barc, Mathieu Leroux-Coyau, Patricia Berthon, Jérôme Chapuis, Christelle Rossignol, Jean-Luc Gatti, Maya Belghazi, Valérie Labas, Jean-Luc Vilotte, Vincent Béringue, Frédéric Lantier, Hubert Laude, and Louis-Marie Houdebine
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6-8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background.
Published: 2015
Full Text: View/download PDF

11. Inhaled bacteriophage therapy in a porcine model of pneumonia caused by <scp> Pseudomonas aeruginosa </scp> during mechanical ventilation

Author: Céline Barc, Mickaël Riou, Yonatan Perez, Antoine Guillon, Jeoffrey Pardessus, Laurent Mereghetti, Elsa Bodier-Montagutelli, Emilie Dalloneau, Camille Thorey, Nathalie Heuzé-Vourc'h, Sandrine Le Guellec, Laurent Vecellio, Maria Cabrera, Youenn Jouan, Guillaume L'Hostis, Cindy Fevre, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pherecydes Pharma, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DTF-Aerodrug, DTF, public grant overseen by the Direction Générale des Armées (DGA)-France - Project RAPID—Pneumophage grant, Chanteloup, Nathalie Katy, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Phage therapy, Swine, medicine.drug_class, medicine.medical_treatment, Antibiotics, medicine.disease_cause, pseudomonas aeruginosa, Microbiology, Bacteriophage, Mice, 03 medical and health sciences, 0302 clinical medicine, bacteriophage, In vivo, medicine, Animals, pneumonia, Bacteriophages, Pseudomonas Infections, Phage Therapy, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, Mechanical ventilation, inhalation, 0303 health sciences, ventilation-associated pneumonia, biology, 030306 microbiology, Pseudomonas aeruginosa, business.industry, biology.organism_classification, medicine.disease, Respiration, Artificial, 3. Good health, Pneumonia, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030228 respiratory system, Lytic cycle, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pseudomonas Phages, business
Abstract: International audience; Background and purpose: Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of pneumonia caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized-phage therapy.Experimental approach: (i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled-phage therapy was evaluated in pigs, which were anesthetized, mechanically ventilated and infected with P. aeruginosa.Key results: By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5 Log reduction, p
Published: 2021
Full Text: View/download PDF

12. Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa

Author: Raquel López-Gálvez, Isabelle Fleurot, Pablo Chamero, Sascha Trapp, Michel Olivier, Claire Chevaleyre, Céline Barc, Mickael Riou, Christelle Rossignol, Antoine Guillon, Mustapha Si-Tahar, Tobias May, Pascal Barbry, Andrea Bähr, Nikolai Klymiuk, Jean-Claude Sirard, Ignacio Caballero
Abstract: Excessive lung inflammation and airway epithelial damage are hallmarks of human inflammatory lung diseases, such as cystic fibrosis (CF). Enhancement of innate immunity provides protection against pathogens while reducing lung-damaging inflammation. However, the mechanisms underlying innate immunity–mediated protection in the lung remain mysterious, in part because of the lack of appropriate animal models for these human diseases. TLR5 (Toll-like receptor 5) stimulation by its specific ligand, the bacterial protein flagellin, has been proposed to enhance protection against several respiratory infectious diseases, although other cellular events, such as calcium signaling, may also control the intensity of the innate immune response. Here, we investigated the molecular events prompted by stimulation with flagellin and its role in regulating innate immunity in the lung of the pig, which is anatomically and genetically more similar to humans than rodent models. We found that flagellin treatment modulated NF-κB signaling and intracellular calcium homeostasis in airway epithelial cells. Flagellin pretreatment reduced the NF-κB nuclear translocation and the expression of proinflammatory cytokines to a second flagellin stimulus as well as toPseudomonas aeruginosainfection. Moreover,invivoadministration of flagellin decreased the severity ofP. aeruginosa–induced pneumonia. Then we confirmed these beneficial effects of flagellin in a pathological model of CF by usingex vivoprecision-cut lung slices from a CF pigz model. These results provide evidence that flagellin treatment contributes to a better regulation of the inflammatory response in inflammatory lung diseases such as CF.
Published: 2021

13. Characterization of the intestinal mononuclear phagocytic cells in the intestine of the lamb to better understand the immune response against Cryptosporidium parvum

Author: Ambre Baillou, Thierry Chaumeil, Céline Barc, Yves Le Vern, Alix Sausset, Schulthess, J., Pauline Peltier-Pain, Sonia Lacroix-Lamandé, Fabrice Laurent, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Phileo Lesaffre Animal Care, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience; Cryptosporidiosis is a poorly controlled zoonosis caused by the intestinal infection by a protozoan parasite, Cryptosporidium parvum (Cp), presenting a high prevalence in ruminant farms (cattle, sheep, goats). Young animals with an immature intestinal immune system are particularly susceptible to this infection. In a neonatal mouse model, we previously demonstrated the key role of innate immunity and in particular of CD11c+CD103+CD11b- dendritic cell (DC) subset incontrolling the acute phase of Cp infection [1]. During infection, in response to chemokine production by infected epithelial cells, newly recruited CD11c+CD103+CD11b- DC produce IL12 and IFNγ contributing to the elimination process of the parasite. According to the current common classification of DC in different species (human, mouse, pig, sheep, and chicken), this subpopulation can be identified as the cDC1 subset of conventional DC. The aim of this project was to better characterize intestinal DC subpopulations in lamb and to determine their role during Cp infection. As in the mouse model, the parasite invades and multiplies mainly in the ileum of young lambs. However, a peculiarity of young ruminants is the presence of a large ileal Peyer’s patch (lymphoid tissue) that extends all along the ileum. We characterized in various compartments of the lamb small intestine (lymphoid and non-lymphoid) the various mononuclear phagocyte populations by performing a phenotypic and functional analysis by flow cytometry and transcriptomic methods respectively. We followed the evolution of the cell subsets according to the age of the animals and during Cp infection. This work represents the first fine description of mononuclear phagocyte cell subsets in the small intestine of young lambs at homeostasis and during the course of C. parvum infection.
Published: 2021

14. Inhaled bacteriophage therapy in a porcine model of ventilator-associated pneumonia caused by pseudomonas aeruginosa

Author: Youenn Jouan, Maria Cabrera, Emilie Dalloneau, Antoine Guillon, Jeoffrey Pardessus, Laurent Vecellio, Elsa Bodier, Guillaume L'Hostis, Laurent Mereghetti, Mickaël Riou, Yonatan Perez, Cindy Fevre, Sandrine Leguellec, Camille Thorey, Céline Barc, and Nathalie Heuzé-Vourc'h
Subjects: biology, Phage therapy, medicine.drug_class, Pseudomonas aeruginosa, business.industry, medicine.medical_treatment, Antibiotics, Ventilator-associated pneumonia, biology.organism_classification, medicine.disease, medicine.disease_cause, Microbiology, Bacteriophage, Pneumonia, Lytic cycle, In vivo, medicine, business
Abstract: Background and Purpose. Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of VAP caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized-phage therapy. Experimental Approach. (i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled-phage therapy was evaluated in pigs, which were anesthetized, mechanically ventilated and infected with P. aeruginosa. Key Results. By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5 Log reduction, p
Published: 2021
Full Text: View/download PDF

15. Evidence of early increased sialylation of airway mucins and defective mucociliary clearance in CFTR-deficient piglets

Author: Catherine Robbe-Masselot, Mustapha Si-Tahar, Ignacio S. Caballero, Renaud Léonard, Nicolas Pons, Andrea Bähr, Pascal Barbry, Antoine Guillon, Agnès Paquet, Claire Chevaleyre, Nikolai Klymiuk, Isabelle Fleurot, Mustapha Berri, Bélinda Ringot-Destrez, Kevin Lebrigand, Carole Baron, Céline Barc, Reuben Ramphal, Isabelle Lantier, Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-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), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de Médecine Intensive et Réanimation [Tours], Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ludwig Maximilian University [Munich] (LMU), Association Vaincre la Mucoviscidose (Grant No. RF20150 501357), Association Grégory Lemarchal (Grant No. RIF20160501690), Fondation pour la Recherche Médicale (DEQ20180339158), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Chanteloup, Nathalie Katy, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université de Tours (UT), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Gene Center and Center for Innovation Medical Models (CiMM), Ludwig Maximilians University of Munich, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Male, Glycosylation, Mucociliary clearance, Swine, [SDV]Life Sciences [q-bio], Sus scrofa, Cystic Fibrosis Transmembrane Conductance Regulator, Context (language use), Inflammation, Respiratory Mucosa, Mucociliary transport, medicine.disease_cause, Cystic fibrosis, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Medicine, Animals, CFTR, ComputingMilieux_MISCELLANEOUS, Lung, medicine.diagnostic_test, business.industry, Pseudomonas aeruginosa, Mucin, Mucins, respiratory system, medicine.disease, 3. Good health, respiratory tract diseases, Trachea, [SDV] Life Sciences [q-bio], Mucin glycosylation, 030104 developmental biology, medicine.anatomical_structure, Bronchoalveolar lavage, 030228 respiratory system, Animals, Newborn, Mucociliary Clearance, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, MESH: CFTR, business
Abstract: International audience; Background: Bacterial colonization in cystic fibrosis (CF) lungs has been directly associated to the loss of CFTR function, and/or secondarily linked to repetitive cycles of chronic inflammation/infection. We hypothesized that altered molecular properties of mucins could contribute to this process.Methods: Newborn CFTR+/+ and CFTR-/- were sacrificed before and 6 h after inoculation with luminescent Pseudomonas aeruginosa into the tracheal carina. Tracheal mucosa and the bronchoalveolar lavage (BAL) fluid were collected to determine the level of mucin O-glycosylation, bacteria binding to mucins and the airways transcriptome. Disturbances in mucociliary transport were determined by ex-vivo imaging of luminescent Pseudomonas aeruginosa.Results: We provide evidence of an increased sialylation of CF airway mucins and impaired mucociliary transport that occur before the onset of inflammation. Hypersialylation of mucins was reproduced on tracheal explants from non CF animals treated with GlyH101, an inhibitor of CFTR channel activity, indicating a causal relationship between the absence of CFTR expression and the sialylation of mucins. This increased sialylation was correlated to an increased adherence of P. aeruginosa to mucins. In vivo infection of newborn CF piglets by live luminescent P. aeruginosa demonstrated an impairment of mucociliary transport of this bacterium, with no evidence of pre-existing inflammation.Conclusions: Our results document for the first time in a well-defined CF animal model modifications that affect the O-glycan chains of mucins. These alterations precede infection and inflammation of airway tissues, and provide a favorable context for microbial development in CF lung that hallmarks this disease.
Published: 2020
Full Text: View/download PDF

16. Novel approaches boosting innate immunity against Pseudomonas aeruginosa

Author: Isabelle Fleurot, Mickael Riou, Claire Chevaleyre, Sandrine Melo, Michel Olivier, Christelle Rossignol, Céline Barc, Jérémy Pezant, Alexis Pleau, Alain Deslis, Nikolai Klymiuk, Jean Claude Sirard, Ignacio Caballero, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Ludwig Maximilians University of Munich, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Société Française de Microbiologie (SFM). FRA., and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Cystic Fibrosis, [SDV.BA]Life Sciences [q-bio]/Animal biology, Pseudomonas aeruginosa, bacteria, TLR5, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Flagellin
Abstract: National audience; Pseudomonas aeruginosa, an opportunistic gram-negative bacterium that rarely infects human lungs unless the host immune system has been impaired, is one of the main pathogens found in cystic fibrosis (CF) patients. P. aeruginosa infections in CF patients are difficult to treat, becoming chronic and contributing to exacerbated lung inflammation and respiratory failure. Modulation of innate immunity has been proposed as an alternative to improve defence against infections. This approach is particularly attractive in CF since exacerbated immune response is central to the pathogenesis of CF lung disease. Innate immunity in epithelial and immune cells can be stimulated through activation of Toll-like receptors (TLRs), the main family of pattern recognition receptors. Stimulation of TLR5 through flagellin-based interventions have demonstrated protective activity against several gram-negative bacteria (Salmonella sp., Burkholderia cepacia, Yersinia pseudotuberculosis), restoring immune-competence and promoting tissue repair processes. Here, we aimed to determine the effect of flagellin stimulation on the innate immune response against P. aeruginosa using an experimental pig model of lung infection. The pig model presents several advantages since swine and human lungs are similar in terms of anatomical, histological, biochemical, and physiological features. This is especially true in CF, where pigs lacking CFTR present a similar phenotype to what is typically observed in human patients. P. aeruginosa-infected pigs showed an acute neutrophilic response with an exacerbated release of neutrophil serine proteases that peaked 3-6 h post-infection (p.i.) leading to lung destruction and tissue hepatisation 24h p.i. When animals were pre-treated with flagellin 24h before the experimental infections, we observed a significant decrease in the expression of pro-inflammatory markers. In addition, a better lung status was observed on infected animals that had been pre-treated with flagellin compared to infected controls. The effect of flagellin pre-treatment on immune response to P. aeruginosa infection was confirmed using ex-vivo and in vitro models of lung epithelium from CFTR-/- pigs. In conclusion, our data point to a modulatory role of flagellin pre-treatment on the immune response to P. aeruginosa. This approach may have a therapeutic potential to improve inflammatory manifestations of CF.
Published: 2019

17. Tetrafunctional Block Copolymers Promote Lung Gene Transfer in Newborn Piglets

Author: Océane Hacquin, Jérémy Pezant, Anne Pinard, Bruno Pitard, Claire Chevaleyre, Julien Fassy, Céline Barc, Mickaël Riou, Georges Vassaux, Roger Rezzonico, Bernard Mari, Ignacio S. Caballero, Nathalie Heuzé-Vourc'h, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), This work was supported by 'Vaincre la Mucoviscidose' (RF20150501439), INSERM, INRA, and the French National Research Agency (ANR grant: ANR-18-CE92-0009-01 - FIBROMIRS)., ANR-18-CE92-0009,FIBROMIR,MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires(2018), Bernardo, Elizabeth, APPEL À PROJETS GÉNÉRIQUE 2018 - MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires - - FIBROMIR2018 - ANR-18-CE92-0009 - AAPG2018 - VALID, 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), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Infectiologie Santé Publique (ISP-311), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Host-pathogen interactions in the regulation of immune responses (CRCINA - Département INCIT - Equipe 5), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), ANR-18-CE92-0009-01,FIBROMIRS,MicroRNAs and Epithelial-Mesenchymal Interactions in Lung Fibrosis, and Vassaux, Georges
Subjects: 0301 basic medicine, copolymère, animal nouveau né, Genetic enhancement, Transgene, newborn pigs, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cystic fibrosis, Article, non-viral vector, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Discovery, Biologie animale, medicine, Cationic liposome, lungs, Animal biology, Lung, tetrafunctional block copolymers, Chemistry, lcsh:RM1-950, Cationic polymerization, medicine.disease, gene therapy, Gene transfer agent, 3. Good health, thérapie génique, 030104 developmental biology, medicine.anatomical_structure, transfert de gène, lcsh:Therapeutics. Pharmacology, 030220 oncology & carcinogenesis, poumon, Biophysics, Molecular Medicine, porcelet, DNA
Abstract: Tetrafunctional block copolymers are molecules capable of complexing DNA. Although ineffective in vitro, studies in mice have shown that the tetrafunctional block copolymer 704 is a more efficient lung gene transfer agent than the cationic liposome GL67A, previously used in a phase II clinical trial in cystic fibrosis patients. In the present study, we compared the gene transfer capacity of the 704-DNA formulation and a cationic liposome-DNA formulation equivalent to GL67A in a larger-animal model, the newborn piglet. Our results indicate an efficacy of the 704-DNA formulation well above one order of magnitude higher than that of the cationic liposome-DNA formulation, with no elevated levels of interleukin-6 (IL-6), taken as a marker of inflammation. Transgene expression was heterogeneous within lung lobes, with expression levels that were below the detection threshold in some samples, while high in other samples. This heterogeneity is likely to be due to the bolus injection procedure as well as to the small volume of injection. The present study highlights the potential of tetrafunctional block copolymers as non-viral vectors for lung gene therapy., Graphical Abstract
Published: 2019
Full Text: View/download PDF

18. Intra-tracheal amikacin spray delivery in healthy mechanically ventilated piglets

Author: Laurent Vecellio, Stephan Ehrmann, Antoine Petitcollin, Gilles Paintaud, Philippe Lanotte, Pierre-François Dequin, Antoine Guillon, Céline Barc, Nathalie Heuzé-Vourc'h, Pierre Sarradin, Bénédicte Cormier, François Darrouzain, Laboratoire de Physico -& Toxico Chimie des systèmes naturels (LPTC), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), DTF-Aerodrug, DTF, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Service de Soins Critiques [Bretonneau], Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Association pour la Promotion à Tours de la Réanimation Médicale, Université de Tours (UT), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Models, Anatomic, Pulmonary and Respiratory Medicine, Drug deposition, Swine, Sprayer, medicine.medical_treatment, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Spray, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, Nebulizer and vaporizer [MeSH], Aerosols [MeSH], Small animal, Antibiotic therapy, medicine, Animals, Pharmacology (medical), 030212 general & internal medicine, Infusions, Intravenous, Amikacin, Lung, Aerosols, Mechanical ventilation, business.industry, Nebulizers and Vaporizers, Biochemistry (medical), respiratory system, Anti-Bacterial Agents, 3. Good health, Trachea, medicine.anatomical_structure, Inhalation, 030228 respiratory system, Anesthesia, Models, Animal, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Intubation, business, Anti-bacterial agents [MeSH], Inhalation [MeSH], medicine.drug, Large animal
Abstract: International audience; Background: Nebulization during mechanical ventilation is impeded by large extra-pulmonary drug deposition and long administration durations which currently limit implementation of inhaled antibiotic therapy. Direct intra-tracheal delivery using a sprayer represents an appealing alternative investigated in small animal models, but large animal data are lacking. Methods: Amikacin was administered through intravenous infusion (20 mg/kg), nebulization (60 mg/kg) and direct intra-tracheal spray (30 mg/kg) to 10 intubated piglets, in a randomized cross-over design. Amikacin concentrations were measured in the serum and pulmonary parenchyma. Anatomic deposition was investigated using immuno-histochemistry. Results: Spray delivery resulted in higher amikacin outputs than nebulization and infusion. Pulmonary inhaled delivery techniques yielded much higher lung concentrations and much lower serum concentrations than intravenous infusion. However, unlike nebulization and infusion, intra-tracheal spray delivery was associated with more than 100-and 1000-fold variability in lung concentrations between and within animals. Amikacin specific immuno-histochemistry showed consistent bronchial and alveolar drug deposition with all modalities. Conclusion: Nebulization remains the most reliable and simple technique to deliver inhaled amikacin uniformly to the lung during mechanical ventilation. Further development of tracheal sprays is required to take advantage of potential benefits related to high drug output and low extra-pulmonary deposition in large animals.
Published: 2019
Full Text: View/download PDF

19. The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin

Author: Edwige Bouguyon, Pierre-Louis Hervé, Nicolas Collin, Olivier Boulesteix, Even Fossum, Charlotte Deloizy, Céline Urien, Tiphany Chrun, Pauline Maisonnasse, Nicolas Bertho, Audrey Duval, Jérémy Pezant, Marc Dalod, Céline Barc, Maelle Codjovi, Christophe Barnier-Quer, Bjarne Bogen, Isabelle Schwartz-Cornil, Christophe Chevalier, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), University of Oslo (UiO), Université de Lausanne = University of Lausanne (UNIL), Plateforme d'Infectiologie Expérimentale (PFIE), Aix Marseille Université (AMU), Agence National de la Recherche grant DCskin-VacFlu [ANR 2011-ISV3-001-01], Research Council of Norway [220642/H10], K.G. Jebsen Foundation, and Université de Lausanne (UNIL)
Subjects: 0301 basic medicine, grippe, Influenza vaccine, Swine, Science, Recombinant Fusion Proteins, [SDV]Life Sciences [q-bio], Monophosphoryl Lipid A, Antibodies, Viral, Virus, Article, Receptors, G-Protein-Coupled, Viral Matrix Proteins, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, immunogenicite, Animals, Intradermal injection, Adjuvants, Immunologic/administration & dosage, Antibodies, Viral/blood, Antibody Formation, Chemokines, C/administration & dosage, Chemokines, C/genetics, Chemokines, C/metabolism, Dendritic Cells/immunology, Dendritic Cells/metabolism, Immunoglobulin G/blood, Influenza Vaccines/administration & dosage, Influenza Vaccines/genetics, Influenza Vaccines/immunology, Oligodeoxyribonucleotides/administration & dosage, Receptors, G-Protein-Coupled/metabolism, Recombinant Fusion Proteins/administration & dosage, Recombinant Fusion Proteins/genetics, Recombinant Fusion Proteins/immunology, Skin/immunology, Skin/metabolism, Viral Matrix Proteins/administration & dosage, Viral Matrix Proteins/genetics, Viral Matrix Proteins/immunology, Skin, Multidisciplinary, biology, Immunogenicity, Dendritic Cells, 3. Good health, Chemokines, C, 030104 developmental biology, CpG site, Oligodeoxyribonucleotides, Influenza Vaccines, Immunoglobulin G, Immunology, anticorps, biology.protein, Medicine, Antibody, porc, 030215 immunology, XCL1
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
Full Text: View/download PDF

20. Fetopathic effects of experimental Schmallenberg virus infection in pregnant goats

Author: Nathalie Pozzi, Eve Laloy, Stéphan Zientara, Cyril Viarouge, Céline Barc, Julie Gouzil, Mickaël Riou, Typhaine Hébert, Maxime Raimbourg, Damien Vitour, Sophie Chateau-Joubert, Rémi Delaunay, Claire Ponsart, Didier Crochet, Benoit Durand, Emmanuel Bréard, Sascha Trapp, Sylvain Breton, Nathalie Cordonnier, Ecole Nationale Vétérinaire d’Alfort, Unité d’anatomie pathologique, Université Paris-Est (UPE), Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Laboratoire National de Contrôle des Reproducteurs (LNCR), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), ANSES, Laboratoire de Santé Animale, European Union (Council decision 2012/349/EU) - General Direction of Food (DGAL,Ministry of Agriculture, France) - Department 'Animal Health' in INRA for studies on Schmallenberg virus, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA), Infectiologie Animale et Santé Publique - IASP (Nouzilly, France), Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: 0301 basic medicine, Orthobunyavirus, infection expérimentale, Placenta, Physiology, 0403 veterinary science, Pregnancy, reproductive and urinary physiology, 2. Zero hunger, Goats, Reproduction, Schmallenberg virus, 04 agricultural and veterinary sciences, General Medicine, 3. Good health, embryonic structures, Goat, Gestation, Female, medicine.symptom, europe, transmission verticale, 040301 veterinary sciences, Offspring, chèvre, Viremia, Biology, Bunyaviridae Infections, Microbiology, Virus, Lesion, 03 medical and health sciences, infection foetale, Fetus, gestation, medicine, Animals, nannygoats, Goat Diseases, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, vertical transmission of disease, transmission virale, mort embryonnaire, medicine.disease, biology.organism_classification, Virology, 030104 developmental biology, experimental infection, virus de Schmallenberg
Abstract: International audience; Schmallenberg virus (SBV) is an emerging virus responsible for congenital malformations in the offspring of domestic ruminants. It is speculated that infection of pregnant dams may also lead to a significant number of unrecognized fetal losses during the early period of gestation. To assess the pathogenic effects of SBV infection of goats in early pregnancy, we inoculated dams at day 28 or 42 of gestation and followed the animals until day 55 of gestation. Viremia in the absence of clinical signs was detected in all virus-inoculated goats. Fetal deaths were observed in several goats infected at day 28 or 42 of gestation and were invariably associated with the presence of viral genomic RNA in the affected fetuses. Among the viable fetuses, two displayed lesions in the central nervous system (porencephaly) in the presence of viral genome and antigen. All fetuses from goats infected at day 42 and the majority of fetuses from goats infected at day 28 of gestation contained viral genomic RNA. Viral genome was widely distributed in these fetuses and their respective placentas, and infectious virus could be isolated from several organs and placentomes of the viable fetuses. Our results show that fetuses of pregnant goats are susceptible to vertical SBV infection during early pregnancy spanning at least the period between day 28 and 42 of gestation. The outcomes of experimental SBV infection assessed at day 55 of gestation include fetal mortalities, viable fetuses displaying lesions of the central nervous system, as well as viable fetuses without any detectable lesion.
Published: 2017
Full Text: View/download PDF

21. The Pig: A Relevant Model for Evaluating the Neutrophil Serine Protease Activities during Acute Pseudomonas aeruginosa Lung Infection

Author: Olivier Boulesteix, Jérémy Pezant, Sylvie Attucci, Christelle Rossignol, Déborah Bréa, Claire Chevaleyre, Francis Gauthier, Patricia Berthon, Sandrine Melo, Michel Olivier, Frédéric Becq, Mickaël Riou, Clarisse Vandebrouck, Mustapha Berri, Ignacio Caballero-Posadas, Mustapha Si-Tahar, Julien Gaillard, Céline Barc, Rémy Delaunay, François Meurens, UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Département des Microscopies, Université Francois Rabelais [Tours], Identités, Cultures, Territoires (ICT (EA_337)), Université Paris Diderot - Paris 7 (UPD7), Bioagression, Epidémiologie et Analyse de Risques (BIOEPAR), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Attucci, Sylvie, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Plateforme d'Infectiologie Expérimentale (PFIE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Morillon, Christelle, Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT), PPF 'Analyses des Systèmes Biologiques', and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Pulmonology, Swine, infection pulmonaire, Pathology and Laboratory Medicine, Cystic fibrosis, Biochemistry, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animal Cells, animal modèle, lcsh:Science, Immune Response, Mammals, Microbiology and Parasitology, protéase, Microbiologie et Parasitologie, 3. Good health, Bacterial Pathogens, Blood, Medical Microbiology, Cytokines, Cellular Types, Bronchoalveolar Lavage Fluid, réponse inflammatoire, Proteases, Livestock, Immune Cells, Immunology, Microbiology, Proinflammatory cytokine, 03 medical and health sciences, Signs and Symptoms, Pseudomonas, Humans, Pseudomonas Infections, Microbial Pathogens, Blood Cells, Bacteria, animal model, lcsh:R, Organisms, Biology and Life Sciences, Proteins, medicine.disease, respiratory tract diseases, 030104 developmental biology, 030228 respiratory system, poumon, lcsh:Q, porc, 0301 basic medicine, Chemokine, Neutrophils, Physiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, White Blood Cells, Pig Models, Medicine and Health Sciences, Multidisciplinary, biology, medicine.diagnostic_test, Pseudomonas Aeruginosa, Agriculture, Animal Models, Hematology, respiratory system, Body Fluids, Enzymes, medicine.anatomical_structure, Vertebrates, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Veterinary medicine and animal Health, medicine.symptom, Chemokines, Pathogens, Anatomy, Research Article, Inflammation, Nose, Research and Analysis Methods, lung, Model Organisms, Diagnostic Medicine, medicine, Animals, Lung, Pseudomonas aeruginosa, Cell Biology, Disease Models, Animal, Médecine vétérinaire et santé animal, Bronchoalveolar lavage, Amniotes, Respiratory Infections, biology.protein, Enzymology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Serine Proteases
Abstract: International audience; The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues. We induced acute neutrophilic inflammatory responses in pig lungs using Pseudomonas aeruginosa, an opportunistic respiratory pathogen. Blood samples, nasal swabs and bronchoalveolar lavage fluids (BALFs) were collected at 0, 3, 6 and 24 h post-insfection (p.i.) and biochemical parameters, serum and BAL cytokines, bacterial cultures and neutrophil activity were evaluated. The release of proinflammatory mediators, biochemical and hematological blood parameters, cell recruitment and bronchial reactivity, peaked at 6h p.i.. We also used synthetic substrates specific for human neutrophil proteases to show that the activity of pig NSPs in BALFs increased. These proteases were also detected at the surface of lung neutrophils using anti-human NSP antibodies. Pseudomonas aeruginosa-induced lung infection in pigs results in a neutrophilic response similar to that described for cystic fibrosis and ventilator-associated pneumonia in humans. Altogether, this indicates that the pig is an appropriate model for testing anti-infectious and/or anti-inflammatory drugs to combat adverse proteolytic effects of neutrophil in human lung diseases.
Published: 2016
Full Text: View/download PDF

22. 99mTc-N-IFC: a new isoniazid derivative for Mycobacterium diagnostic

Author: Sihem Guizani, Najoua Mejri, Mouldi Saidi, Salem Ben Hamouda, Imen Essouissi, Amin Asmi, Céline Barc, Serge Bernard, and Nadia Malek Saied
Subjects: biology, Chemistry, Isoniazid, biology.organism_classification, Combinatorial chemistry, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, 030212 general & internal medicine, Physical and Theoretical Chemistry, Derivative (chemistry), Mycobacterium, medicine.drug
Abstract: We present in this work a new technetium-99m-labeled derivative from isoniazid. The labeling was achieved with a double-ligand transfer through the use of a ferrocene derivative. A further referred to as 99mTc-N-IFC (N-Isonicotinamide ferrocene carboxamide labeled with 99mTc), targeting infections in experimental animals, has been synthesized. The N-IFC was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it was obtained with high radiolabelling yield (95%). Radiochemical analyses of 99mTc-N-IFC revealed that the molecule was efficiently labeled with a little free pertechnetate in the preparations containing purified compound. Only 1–2% of the tracer was leached out from the complex at 24 h when incubated in serum at 37 ºC confirmed its high stability. The radiolabeled complex was found to be 10% bound to blood protein, which corresponds to a fast retention advantage. Biodistribution study showed the renal route of excretion and has also demonstrated that our radiolabeled compound is rapidly and significantly accumulated (P) at infection sites. Thigh model of localized infection was prepared in mice by injecting of BCG (pGFM-11) (fluorexcente BCG) live bacteria in growing phase. The confirmation of the bacteria presence in infection sites has been established through its fluorescence characteristic. The comparison of the 99mTc-N-IFC accumulation at sites of BCG (pGFM-11) infected animals, which is expressed as target-to-non-target ratio, (3.14) with other radiotracers was discussed. This allowed us to consider that 99mTc-N-IFC could be a good radiotracer for mycobacterial infections. Obtained results were in good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work.
Published: 2011
Full Text: View/download PDF

23. Semen from scrapie-infected rams does not transmit prion infection to transgenic mice

Author: Céline Lecomte, Jean-Louis Dacheux, Sandrine Melo, Olivier Andreoletti, Jean-Luc Gatti, Céline Barc, Pierre Sarradin, Frédéric Lantier, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Embryology, Sexual transmission, Genotype, PrPSc Proteins, animal diseases, medicine.medical_treatment, Gene Expression, Mice, Transgenic, Semen, Scrapie, Biology, Injections, PRNP, Mice, 03 medical and health sciences, Endocrinology, Disease Transmission, Infectious, medicine, Animals, Insemination, Artificial, Sheep, Domestic, 030304 developmental biology, 2. Zero hunger, Infectivity, 0303 health sciences, Transmissible spongiform encephalopathy, Artificial insemination, 030302 biochemistry & molecular biology, Brain, Obstetrics and Gynecology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, medicine.disease, Virology, nervous system diseases, 3. Good health, Reproductive Medicine, Models, Animal, Horizontal transmission
Abstract: Scrapie is the most common transmissible spongiform encephalopathy (TSE) in livestock. Natural contamination in sheep flocks is presumed to occur by maternal transmission to offspring. However, horizontal prion transmission from animal to animal exists and may be significant in sustaining and spreading contagion in the field. Artificial insemination is widely used in modern farming, and as large amounts of prion protein have been found in sheep sperm membrane, epididymal fluid and seminal plasma, horizontal transmission by this route was hypothesized since no clear information has been obtained on possible sexual transmission of TSE. We therefore tested the contamination levels of semen from scrapie-infected rams at different stages of incubation, including the clinical phase of the disease. We report here that under our experimental conditions ram semen did not transmit infectivity to scrapie-susceptible transgenic mice overexpressing the V136R154Q171 allele of the sheep prion (PRNP) gene. These results suggest that artificial insemination and natural mating have a very low or negligible potential for the transmission of scrapie in sheep flocks.
Published: 2008
Full Text: View/download PDF

24. IMPY, a potential β-amyloid imaging probe for detection of prion deposits in scrapie-infected mice

Author: Hank F. Kung, Sylvie Chalon, Pu-Jiao Song, Céline Barc, Denis Guilloteau, Serge Bernard, Mei-Ping Kung, Jackie Vergote, Pierre Sarradin, Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), and University of Pennsylvania
Subjects: Cancer Research, IMPY, Amyloid, Prions, medicine.drug_class, [SDV]Life Sciences [q-bio], animal diseases, Plaque, Amyloid, Scrapie, Monoclonal antibody, Binding, Competitive, 030218 nuclear medicine & medical imaging, Iodine Radioisotopes, Mice, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Animals, Humans, PRION DISEASES, Radiology, Nuclear Medicine and imaging, Radionuclide Imaging, Binding selectivity, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, Chemistry, Antibodies, Monoclonal, Brain, Ligand (biochemistry), Virology, Molecular biology, Imaging agent, In vitro, Disease Models, Animal, Isotope Labeling, Autoradiography, Pyrazoles, Molecular Medicine, Radiopharmaceuticals, AMYLOID IMAGING PROBE, AUTORADIOGRAPHY, Preclinical imaging
Abstract: International audience; Introduction: A potential single-photon emission computed tomography imaging agent for labeling of A beta plaques of Alzheimer's disease, IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), would be effective in detection of prion amyloid deposits in transmissible spongiform encephalopathies (TSEs). Methods: In vitro autoradiographic studies were carried out with [I-125]IMPY on brain sections from scrapie-infected mice and age-matched controls. Competition study was performed to evaluate the prion deposit binding specificity with nonradioactive IMPY. Results: Binding of [I-125]IMPY was observed in infected brain sections, while on age-matched control brain sections, there was no or very low labeling. Prion deposit binding was confirmed by histoblots with prion protein-specific monoclonal antibody 2D6. In the presence of nonradioactive IMPY, the binding of [I-125]IMPY was significantly inhibited in all regions studied. Conclusions: These findings indicate that IMPY can detect the prion deposits in vitro in scrap ie-infected mice. Labeled with I-123, this ligand may be useful to quantitate prion deposit burdens in TSEs by in vivo imaging. (c) 2008 Elsevier Inc. All rights reserved.
Published: 2008
Full Text: View/download PDF

25. A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies

Author: Olivier Boulesteix, Peter Sebo, Isabelle Schwartz-Cornil, Bruno Da Costa, Claude Leclerc, Ondrej Stanek, Cindy Bernelin-Cottet, Luc Jouneau, Charles-Adrien Richard, Edwige Bouguyon, Charlotte Deloizy, Céline Barc, Nicolas Bertho, Christophe Chevalier, Jérémy Pezant, Mohammed Moudjou, Céline Urien, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Institute of Microbiology, Czech Academy of Sciences [Prague] (CAS), Plateforme d'Infectiologie Expérimentale (PFIE), Régulation Immunitaire et Vaccinologie, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Agence National de la Recherche grant DCskin-VacFlu, ANR 2011-ISV3-001-01 (CD, EB, NB, IS-C) - grants M200201213 of the CAS (PS) - TA03010331 of TACR (PS) - QJ1210041 of MZe (OS) of the Czech Republic., Schwartz-Cornil, Isabelle, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and ProdInra, Archive Ouverte
Subjects: 0301 basic medicine, vaccin, [SDV.IMM] Life Sciences [q-bio]/Immunology, Influenza vaccine, medicine.drug_class, Immunology, Biology, medicine.disease_cause, Monoclonal antibody, interdigitating cell, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, 0302 clinical medicine, Antigen, Immunity, vaccine, Immunologie, Influenza A virus, medicine, Immunology and Allergy, dendritic cells, human, Viral shedding, Original Research, mode d'administration, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Correction, human influenza, swine, Dendritic cell, routes of administration, vaccines, Virology, 3. Good health, Vaccination, Vaccinology, 030104 developmental biology, Médecine vétérinaire et santé animal, Vaccinologie, influenza, [SDV.IMM]Life Sciences [q-bio]/Immunology, Veterinary medicine and animal Health, cellule dendritique, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, 030215 immunology, porc
Abstract: Corrigendum dans Front Immunol. 2017; 8: 831. The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fimmu.2016.00641/full#supplementary-material; 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
Full Text: View/download PDF

26. Neutrophils in cystic fibrosis. Are they intrinsically defective?

Author: Deborah Brea, Laura Soler Vasco, Antoine Guillon, Claire Chevaleyre, Céline Barc, Mustapha Berri, Michel Olivier, Sandrine Melo, Isabelle Fleurot, Jérémy Pezant, Valérie Labas, Ana Paula Teixeira, Pierre Sarradin, Mickaël Riou, Nikolai Klymiuk, Mustapha Si-Tahar, Ignacio Caballero-Posadas, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Gene Center and Center for Innovative Medical Models (CIMM), ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs]
Abstract: National audience; Cystic fibrosis (CF) is a recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF lungs are characterized by chronic colonization by opportunistic pathogens and a neutrophilic infiltration that results in excessive neutrophil protease release and lung tissue destruction. Previous studies have reported neutrophil dysfunction in CF. However, the exact etiology of the altered functionality of CF neutrophils (i.e.a result of the genetic defect or a consequence of chronic infection, remains unclear. Recently, a CFTR-/- knockout pig model has been developed that displays most of the features of the human CF disease1. We and others have shown that at birth these animals do not show early signs of systemic or lung infection. This fact and the similarities between human and pig neutrophils3 make them a suitable model to develop a research project aimed to answer the following key question: are CF neutrophils intrinsically defective? Blood neutrophils will be collected from CFTR-/- and wild-type (WT) newborn piglets and differences in their proteomic profiling will be evaluated using Intact Cell MALDI-TOF MS (ICM-MS). MS spectra will be further processed and analyzed with ClinProTools v3.0. Our preliminary data shows that ICM-MS-based analysis discriminates CFTR-/- and WT neutrophils suggesting differences in their protein composition. Further analysis will include the characterization of the molecular composition of the spectra through high-throughput top-down protein by nanoLC-MS/MS on a LTQ Orbitrap Velos. Functional assays will be performed on neutrophils in order to establish a link between differentially-expressed proteins and neutrophil activity. The expected data could provide a molecular target for CF therapies modulating neutrophil function.
Published: 2015

27. Schmallenberg in vivo à la PFIE

Author: Mickaël Riou, Pierre Sarradin, Didier Crochet, Céline Barc, Rémi Delaunay, Sylvain Breton, Sascha Trapp, Thierry Pineau, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Département Santé Animale (DEPT SA), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES). Maisons-Alfort, FRA. Réseau Français pour la Santé Animale (RFSA), FRA., and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2015

28. Computed Tomography (CT) Scanning Facilitates Early Identification of Neonatal Cystic Fibrosis Piglets

Author: Patricia Berthon, Reuben Ramphal, Joseph Moënne-Loccoz, Andrea Bähr, Pierre Sarradin, François Lecompte, Sylvie Attucci, Ignacio S. Caballero, Mustapha Si-Tahar, Thierry Villemagne, Rémi Delaunay, Nikolai Klymiuk, Mustapha Berri, Antoine Guillon, Céline Barc, Jérémy Pezant, Claire Chevaleyre, Dominique Buzoni-Gatel, Hans Adriaensen, Eckhard Wolf, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation polyvalente, Groupe Hospitalier Paris Saint-Joseph, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Plateforme CIRE, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service anesthésie-réanimation, Gene Center and Center for Innovative Medical Models (CIMM), Foundation Vaincre la Mucoviscidose RF20130500925, Region Centre 32000604, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie Animale et Santé Publique - IASP (Nouzilly, France), Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Paris Saint-Joseph (hpsj), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and ProdInra, Archive Ouverte
Subjects: Male, pig, Pathology, Cystic Fibrosis, Swine, medicine.medical_treatment, Cystic Fibrosis Transmembrane Conductance Regulator, lcsh:Medicine, Computed tomography, ileostomy, Gastroenterology, Cystic fibrosis, 0302 clinical medicine, fluids and secretions, maladie génétique, lcsh:Science, fibrose cystique, 0303 health sciences, Gastrointestinal tract, Multidisciplinary, biology, medicine.diagnostic_test, sucking pig, respiratory system, Cystic fibrosis transmembrane conductance regulator, 3. Good health, 030220 oncology & carcinogenesis, histopathology, Female, porcelet, Autre (Sciences du Vivant), Research Article, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], congenital, hereditary, and neonatal diseases and abnormalities, Genotype, Meconium Ileus, ileostomie, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Ileostomy, tomodensitométrie, genetic disease, Intensive care, Internal medicine, medicine, Animals, porcin, 030304 developmental biology, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], business.industry, histopathologie, lcsh:R, medicine.disease, digestive system diseases, Animals, Newborn, Nuclear medicine, biology.protein, Histopathology, lcsh:Q, business, Tomography, X-Ray Computed, Médecine nucléaire
Abstract: Background Cystic Fibrosis (CF) is the most prevalent autosomal recessive disease in the Caucasian population. A cystic fibrosis transmembrane conductance regulator knockout (CFTR-/-) pig that displays most of the features of the human CF disease has been recently developed. However, CFTR -/- pigs presents a 100% prevalence of meconium ileus that leads to death in the first hours after birth, requiring a rapid diagnosis and surgical intervention to relieve intestinal obstruction. Identification of CFTR -/- piglets is usually performed by PCR genotyping, a procedure that lasts between 4 to 6 h. Here, we aimed to develop a procedure for rapid identification of CFTR -/- piglets that will allow placing them under intensive care soon after birth and immediately proceeding with the surgical correction. Methods and Principal Findings Male and female CFTR +/- pigs were crossed and the progeny was examined by computed tomography (CT) scan to detect the presence of meconium ileus and facilitate a rapid post-natal surgical intervention. Genotype was confirmed by PCR. CT scan presented a 94.4% sensitivity to diagnose CFTR -/- piglets. Diagnosis by CT scan reduced the birth-to-surgery time from a minimum of 10 h down to a minimum of 2.5 h and increased the survival of CFTR -/- piglets to a maximum of 13 days post-surgery as opposed to just 66 h after later surgery. Conclusion CT scan imaging of meconium ileus is an accurate method for rapid identification of CFTR -/- piglets. Early CT detection of meconium ileus may help to extend the lifespan of CFTR -/- piglets and, thus, improve experimental research on CF, still an incurable disease.
Published: 2015
Full Text: View/download PDF

29. Aerosol Route to Administer Teicoplanin in Mechanical Ventilation: In Vitro Study, Lung Deposition and Pharmacokinetic Analyses in Pigs

Author: Laurent Vecellio, Pierre Sarradin, Céline Barc, Nathalie Heuzé-Vourc'h, Patrice Diot, François Darrouzain, Mustapha Si-Tahar, Philippe Lanotte, Eve Haguenoer, Antoine Guillon, Emmanuelle Mercier, Université Francois Rabelais [Tours], Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation polyvalente, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Service de Bactériologie–Virologie, Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: Models, Anatomic, Swine, aerosol, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antibiotics, Pharmaceutical Science, 0302 clinical medicine, Drug Stability, Pharmacology (medical), Respiratory system, Lung, Teicoplanin, Chemistry, Ventilator-associated pneumonia, Equipment Design, Glycopeptide, 3. Good health, Anti-Bacterial Agents, glycopeptide, medicine.anatomical_structure, Anesthesia, Injections, Intravenous, Models, Animal, pharmacokinetics, medicine.drug, Half-Life, Pulmonary and Respiratory Medicine, Staphylococcus aureus, medicine.drug_class, Cell Line, 03 medical and health sciences, ventilator-associated pneumonia, Pharmacokinetics, Administration, Inhalation, medicine, Animals, Particle Size, Radionuclide Imaging, Mechanical ventilation, Aerosols, Nebulizers and Vaporizers, 030208 emergency & critical care medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, bacterial infections and mycoses, Respiration, Artificial, carbohydrates (lipids), 030228 respiratory system, Feasibility Studies, bacteria
Abstract: International audience; Backround: Glycopeptides given intravenously achieve low airway concentrations. Nebulization of teicoplanin may be an efficient way of delivering a high concentration of this antibiotic to the lung. This multistep study assessed the feasibility of teicoplanin nebulization during mechanical ventilation by evaluating: the stability of its antibiotic effect; epithelial tolerance; lung deposition and systemic absorption in ventilated pigs. Nebulized and non-nebulized teicoplanin activity was tested on Staphylococcus aureus cultures. The cytotoxic effect of teicoplanin on human respiratory epithelial cells was assessed by measuring lactate dehydrogenase activity released, cell viability, and transepithelial electrical resistance. Volume median diameter of particles of nebulized teicoplanin was measured by laser diffraction during mechanical ventilation. The deposited mass of teicoplanin nebulized with a vibrating mesh nebulizer in ventilated piglets was assessed by scintigraphy. Blood pharmacokinetics of teicoplanin administered either intravenously or by nebulization was compared. No decrease of antibiotic activity was observed after nebulization. In vitro cytotoxicity of teicoplanin was only observed with 1000 times the dose recommended for intravenous administration. Volume median diameter of particles was 2.5±0.1 μm. Of the initial nebulizer charge of teicoplanin, 24±7% was present in the lungs of ventilated pigs after the nebulization. Amount absorbed in blood was low (3.4%±0.9%) after nebulization, and blood stream elimination half-life value was 25.4 h. Teicoplanin was administered efficiently by nebulization during mechanical ventilation, without any effect on its pharmacological properties or any cytotoxicity. The pharmacokinetic parameters are promising in view of its time-dependent killing process. All the results of our multi-step study highlighted the potential of teicoplanin to be nebulized during mechanical ventilation.
Published: 2015
Full Text: View/download PDF

30. Transgenic rabbits expressing ovine PrP are susceptible to scrapie

Author: Nathalie Daniel-Carlier, Maya Belghazi, Christelle Rossignol, Céline Barc, Pierre Sarradin, Louis-Marie Houdebine, Claude Limouzin, Vincent Béringue, Valérie Labas, Jean-Luc Gatti, Jérôme Chapuis, Jean Luc Vilotte, Frédéric Lantier, Patricia Berthon, Hubert Laude, Olivier Andreoletti, Mathieu Leroux-Coyau, Celine Viglietta, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut Sophia Agrobiotech (ISA), Institut National de la Recherche Agronomique (INRA)-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)-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plate-forme d'Analyse Intégrative des Biomolécules, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), UR Infectiologie animale et Santé publique (UR IASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Tours, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Archive Ouverte, Sarradin, Pierre, and Beringue, Vincent
Subjects: Male, animal diseases, Scrapie, Mass Spectrometry, Animals, Genetically Modified, 0302 clinical medicine, résistance aux agents pathogènes, Biology (General), Pathogen, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Veterinary diseases, 3. Good health, Veterinary medicine and animal Health, animal transgénique, Female, Rabbits, Brain diseases, expérimentation, Research Article, Gene isoform, QH301-705.5, Prions, Transgene, Immunoblotting, Molecular Sequence Data, Immunology, Biology, Microbiology, PRNP, 03 medical and health sciences, Species Specificity, Virology, Genetics, Animal prion diseases, Animals, PrPC Proteins, lapin, Amino Acid Sequence, Allele, Molecular Biology, Gene, encéphalopathie spongiforme transmissible, 030304 developmental biology, Sheep, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Genetically modified animals, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Wild type, RC581-607, barrière d'espèce, nervous system diseases, Médecine vétérinaire et santé animal, protéine prion, Parasitology, Immunologic diseases. Allergy, 030217 neurology & neurosurgery
Abstract: Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6–8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background., Author Summary Prions are infectious pathogens causing irremediably fatal neurodegenerative diseases in human and in farmed or wild animals. They are formed from abnormally folded assemblies (PrPSc) of the host-encoded prion protein (PrPC). Different PrPSc conformational variants or ‘strains’ can propagate in the same host, giving distinct biological phenotypes. Like other pathogens, prions can transmit from one species to another, representing a zoonotic risk. A barrier, commonly referred to as “species barrier”, limits prion cross-species transmission. This barrier is supposed to reflect the steric incompatibility between invading prion PrPSc and PrPC of the infected host. Rabbit is one of the species that exhibit a pronounced resistance to prions. To gain insights on the molecular determinants of the relative resistance of this species to prions, we generated transgenic rabbits expressing sheep PrPC and assessed their experimental susceptibility to sheep scrapie prions, as routinely done with transgenic mouse models of prion disease. All transgenic rabbits developed a typical prion disease within 200 days, whereas wild type rabbits remained healthy more than 700 days after inoculation. These data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background.
Published: 2015
Full Text: View/download PDF

31. An evaluation of a new single-use flexible bronchoscope with a large suction channel: reliability of bronchoalveolar lavage in ventilated piglets and initial clinical experience

Author: L. Guilleminault, Thierry Boulain, Antoine Guillon, Pierre-François Dequin, Stephan Ehrmann, M. Ferrandière, J. Mankikian, T. Le Fol, and Céline Barc
Subjects: Suction (medicine), medicine.medical_specialty, Swine, Suction, Bronchoalveolar Lavage, Intensive care, Surveys and Questionnaires, Bronchoscopy, Medicine, Animals, Flexible bronchoscopy, Single use, medicine.diagnostic_test, business.industry, Reproducibility of Results, Satisfaction questionnaire, Equipment Design, Respiration, Artificial, Surgery, Anesthesiology and Pain Medicine, Channel reliability, Bronchoalveolar lavage, Bronchoscopes, Anesthesia, Quality of vision, business
Abstract: A single-use flexible bronchoscope with a large suction channel has become available recently and we have evaluated this innovative device. Firstly, bronchoalveolar lavage was performed and quantified in ventilated piglets. Next, the bronchoscope was evaluated in three intensive care units and a satisfaction questionnaire was carried out. Sixteen bronchoalveolar lavages were performed in piglets with a recovery rate of 83 (79-86 [72-89])% of the instilled volume. Quality and performance of all devices tested was identical. The medical satisfaction questionnaire was as follows: 'acceptable' to 'very good' for quality of aspiration, manoeuvrability and quality of vision; 'very good' to 'perfect' for setting up and insertion. This encouraging preliminary evaluation demonstrates the effectiveness of this new single-use device, which may obviate the need for disinfection procedures and, thereby, eradicate a potential vector of patient cross-contamination.
Published: 2014

32. Contribution of computed tomography (CT) scan to extend the lifespan of a porcine CFTR - / - model

Author: Ignacio Caballero, Antoine Guillon, Céline Barc, El Mostafa Berri, Claire Chevaleyre, Sandrina Melo, Deborah Brea, Mickaël Riou, Francois Meurens, Jérémy Pezant, Coigné, J., Hans Adriaensen, François Lecompte, Eric Venturi, Lardy, H., Villemagne, T., Moënne-Loccoz, J., Nathalie Winter, Francis Gauthier, Bertrand Schwartz, Bärh, A., Wolf, E., Nikolai Klymiuk, Ramphal, R., Pierre Sarradin, Mustapha Si-Tahar, Dominique Buzoni, ProdInra, Migration, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation polyvalente, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Service anesthésie-réanimation, Gene Center, LMU, Association Vaincre la Mucovisidose (VLM), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2014

33. Développement d'un modèle d'infection respiratoire aiguë à Pseudomonas aeruginosa chez le porc

Author: Mickaël Riou, Claire Chevaleyre, Deborah Brea, Céline Barc, Clarisse Vandebrouck, Jérémy Pezant, Sandrine Melo, Olivier Boulesteix, Michel Olivier, Alexis Pléau, Antoine Guillon, Christelle Rossignol, Hervé Le Roux, Patricia Berthon, Valérie Quesniaux, Frédéric Becq, Ramphal, R., Pierre Sarradin, Dominique Buzoni, Mustapha Si-Tahar, François Meurens, Sylvie Attucci, Ignacio Caballero, El Mostafa Berri, ProdInra, Migration, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Université Francois Rabelais [Tours], Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Service de réanimation polyvalente, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), UMR7355 Immunologie et Neurogénétique Expérimentales et Moléculaires, Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Vaccine and Infecious Disease Organization - International Vaccine Center, Partenaires INRAE, University of Saskatchewan, Association Vaincre la Mucovisidose (VLM), Fédération de la Recherche en Infectiologie. FRA., Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: National audience; Objet de l’étude : Pseudomonas aeruginosa (P.a) est une bactérie opportuniste ayant une responsabilité majeure dans les infections respiratoires comme la mucoviscidose ou les pneumonies acquises sous ventilation mécanique. La colonisation des poumons par P.a chez les patients mucoviscidosiques induit une réponse inflammatoire importante, avec un large recrutement de neutrophiles. Ce projet consiste à mettre en place un modèle d’infection à P.a chez le porc afin de caractériser la réponse immunitaire innée précoce. Les paramètres mesurés ont été : (i) la clairance bactérienne pulmonaire, (ii) le recrutement des populations cellulaires (iii) l’activité des protéases à sérine neutrophiliques, (iv) la réponse cytokinique, (v) la réactivité des bronches et (vi) les lésions pulmonaires. Méthodes : Le schéma expérimental retenu a été le suivant : 12 porcs (LW, 2 mois) ont été inoculés par instillation endotrachéale avec 70 ml de PBS seul (n=6) ou contenant 8x106 ufc/ml de P.a (n=6). La numération sanguine a été réalisée aux points H0, H6 et H24 p.i.. Parallèlement, différents lavages broncho-alvéolaires (LBA) ont été réalisés afin d'évaluer le recrutement des différentes populations cellulaires, de quantifier les cytokiniques pro-inflammatoires et de mesurer l'activité des sérines protéases neutrophiliques. L’impact de l’infection a également été mesuré sur l’activité mécanique bronchique, sur les lésions tissulaires et par numération bactérienne sur les LBA et les tissus pulmonaires. Résultats : L'infection par P.a induit des modifications cliniques dès 6h (fièvre, augmentation de la fréquence respiratoire). Elle modifie les proportions cellulaires sanguines et pulmonaires. Une augmentation des neutrophiles (39%) accompagnée d’une diminution (44%) des lymphocytes est observée significativement à 6h (p104 ufc/ml) 6h après l'inoculation, puis une clairance à 24 h. Conclusions : P.a. induit une réponse immunitaire inflammatoire précoce chez le porc avec un pic de recrutement de neutrophiles dans le parenchyme pulmonaire et dans le sang à 6h, et une clairance du pathogène à 24h. La mise en place d’un modèle expérimental d'infection aiguë à P.a constitue ainsi un outil indispensable pour étudier la mucoviscidose dans sa composante inflammatoire. Ce modèle d’infection pourra être notamment transposé aux porcs dépourvu du gène CFTR, disponible à l’INRA de Tours.
Published: 2014

34. Preliminary studies for the establishment of a model of lung colonization caused by Pseudomonas aeruginosa in piglets - Perspectives of application in the CFTR-deficient piglets

Author: Claire Chevaleyre, Mickaël Riou, El Mostafa Berri, Juliette Cognie, Eric Venturi, Lardy, H., Villemagne, T., Moënne-Loccoz, J., Nathalie Winter, Gauthier, F., Bertrand Schwartz, Bahr, A., Wolf, E., Ramphal, R., Attucci, S., Dominique Buzoni-Gatel, Si-Taha, M., Pierre Sarradin, Brea, D., Michel Olivier, Antoine Guillon, Francois Meurens, Céline Barc, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), service de Chirurgie Pediatrique, Hôpital Gatien de Clocheville, service de Réanimation Médicale, Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM), Gene Center, LMU, Société de Pneumologie de Langue Française (SPLF). Paris, FRA., Association Vaincre la Mucoviscidose - Conseil Regional «Centre» et Cluster d'lnfectiologie de la Region Centre, Vaincre la Mucoviscidose. Paris., ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], inflammation, infection
Abstract: National audience; Introduction: Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the Cystic Fibrosis Trans membrane conductance Regulator (CFTR) gene. The lack of an animal model with lung abnormalities similar to those typically found in human CF has hindered studies of pathogenesis, treatment and prevention of infection in this disease. We aim to establish in Tours a CF pig model with a mutant CFTR that was engineered by our collaborator E. Wolf (Gene Center, LMU, Munich, Germany). Methods: Pigs with mutant CFTR are bred in Tours, France. One difficulty with this CF pig model is a 100% prevalence of meconium ileus leading to death in the first days of birth. We therefore organized a multidisciplinary team at Tours (Inserm-INRA-CHU of Tours) and produced animals by mating CFTR+/- male and female pigs. Newborn CF piglets were anesthetized for surgical procedure after the diagnosis of CFTR-/- was confirmed by PCR. Prior to surgery, an attempt to diagnose the intestinal obstruction by abdominal ultrasonography and computerized tomography (CT) scan was made. Results: Eleven CFTR -/- piglets (1.2 ± 0.2 kg) were born from Nov 2012 to Apr 2013. Nine of them were anesthetized for exploratory laparotomy; the two others were stillborn or euthanized (moribund). The mean birth-to-surgery time was 12.9 ± 2.8 h and included the time for PCR analysis. All CFTR -/- piglets developed meconium ileus, with distended intestine proximal to the obstruction and had poorly developed colon (microcolon). Four piglets had non-viable lesions (intestinal perforation). Ileostomies (intestinal by-pass) were performed for the setting-up of the anesthesia and surgical procedures, but the piglets were eventually euthanized. Finally, five piglets were waking up with an ileostomy. In addition to post-operative care, maternal-milk bottle-feeding has been started six hours after the surgery, with feces passing through the ileostomy. They survived one to three days. We failed to identify the meconium ileus by ultrasonography, but succeed by CT scan. A wide variety of tissues/fluids were collected from these animals to begin a tissue/secretion samples bank for future studies. Conclusions: The cause of death of the CFTR KO piglets is not currently known, and we are still improving the post-operative cares. As the incidence of meconium ileus is of 100% in CFTR -/- animals, the diagnosis could be done faster by CT scan (and confirmed later by the PCR). By reducing the birth-to-surgery time, we hope to improve the survival. The tissues that we have collected provide an original opportunity to investigate initiating mechanisms of disease, with CF and non-CF comparisons, but without confounders.
Published: 2013

35. Techniques d’administration d’aérosols de médicaments chez l’animal

Author: Antoine Guillon, Laurent Vecellio, Jerome Montharu, Céline Barc, Valérie Schubnel, Georges Roseau, Michèle de Monte, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), DTF-Aerodrug, DTF, Université Francois Rabelais [Tours], Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration
Subjects: aérosol, inhalation, modèle animal, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, poudre, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT]
Abstract: National audience; L'article s'intéresse aux techniques d'administration d'aérosols médicamenteux chez l'animal. Ces techniques sont développées lors d'études précliniques visant à tester l'efficacité de drogues à visée pulmonaire, mais également de médicaments agissant par voie sanguine, à évaluer leur cinétique, leur tolérance pulmonaire et/ou leur toxicité. Nous avons choisi d'exposer cette problématique particulière en trois parties principales : 1) Nous présentons les différentes techniques permettant de produire des aérosols médicamenteux liquides ou solides (poudres). 2) Nous exposons les particularités anatomiques et physiologiques de l'appareil respiratoire de la souris, du rat, du porc, du primate non humain et de l'homme, et l'impact de leurs spécificités sur l'administration des aérosols médicamenteux. 3) Nous détaillons les techniques d'inhalation pré-cliniques standards et nous décrivons des techniques d'administration d'aérosols adaptées, développées au laboratoire avec des modèles de rongeurs, de primates et de porcs. Nous discutons leur pertinence pour la réalisation d'études ciblées.
Published: 2013

36. Le système de management de la qualité : un outil précieux pour la gestion du risque biologique dans les installations de haute sécurité utilisées en infectiologie expérimentale

Author: Pierre Sarradin, Nelly Rouet, Olivier Boulesteix, Coralie Gimenez, Céline Barc, Nathalie Kasal-Hoc, Céline Housseau, Bertrand Schwartz, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Département Santé Animale (DEPT SA), Association Française des Sciences et Techniques de l'Animal de Laboratoire (AFSTAL). Paris, FRA., and ProdInra, Migration
Subjects: sécurité biologique, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, infectiologie animale, OGM, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Certification ISO 9001, MOT, sûreté biologique, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2012

37. Gene transfer strategy to promote axonal regeneration in the injured spinal cord : towards clinical application

Author: Lecomte, M. J., Desclaux, M., Chan Seng, E., Lonjon, N., Do Thi, A., Héloïse Pilet, Ursulet, S., Altemir, D., Mickaël Riou, Céline Barc, David Gauthier, Jérémy Pezant, Pierre Sarradin, Sarkis, C., Arnault Privat, Mallet, J., Perrin, F., NewVectys, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Physiopathology and Treatment of Neurodegenerative disorders, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS), Ikerbasque - Basque Foundation for Science, University of the Basque Country, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Migration
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, transduction
Abstract: Session : Viral Vectors; International audience; In spinal cord injury (SCI), reactive astrocytes build-up a dense cellular structure, the glial scar, that forms both physical and chemical barriers considered to be detrimental for axonal regeneration. Reactive astrocytes present hypertrophic processes resulting mainly from increased expression of glial fibrillary acidic protein (GFAP) and vimentin, two astrocyte cytoskeletal intermediate filament proteins. It had been shown, in mice knockout for both GFAP and vimentin, that due to the absence of glial reactivity, reinnervation and partial motor recovery occurred after lateral spinal cord hemisection. In order to translate this proof of principle into a therapeutic strategy, we have developed an experimental approach based on the use of siRNA carried by lentiviral vectors. We have developed lentiviral vectors Lv-siGFAP and Lv-siVIM which inhibit the in vitro formation of a glial scar in a Scratch model of lesion. Here we report that in a mouse model of SCI, intraspinal application of Ientiviral vectors Lv-shGFAP and Lv-shVIM efficiently reduces glial reactivity by silencing GFAP alone or associated with vimentin, permits axonal regrowth and improves functional motor recovery. With the objective of translation to clinics, we are adapting the work performed on mice to a large animal model (domestic swine), in order to mimic the clinical settings. We thus first designed and generated lentiviral vectors Lv-siGFAPsw able to inhibit GFAP expression in swine astrocytes. In parallel, we started to define the experimental surgical procedures of lentiviral transduction in the swine injured spinal cord by hemisection.
Published: 2011

38. Teicoplanin Aerosol In Mechanical Ventilated Piglets: Lung Deposition And Pharmacokinetic Study

Author: Patrice Diot, Laurent Vecellio, Céline Barc, Antoine Guillon, Pierre Sarradin, Emmanuelle Mercier, Jérôme Montharu, U618, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Francois Rabelais [Tours], Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), and American Thoracic Society. USA.
Subjects: Chromatography, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Pharmacokinetics, Lung deposition, Teicoplanin, Chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, medicine, ComputingMilieux_MISCELLANEOUS, 3. Good health, Aerosol, medicine.drug
Abstract: International audience
Published: 2011
Full Text: View/download PDF

39. Evaluation of Prion Deposits and Microglial Activation in Scrapie-Infected Mice Using Molecular Imaging Probes

Author: Nicolas Arlicot, Denis Guilloteau, Serge Bernard, Pu-Jiao Song, Lucette Garreau, Céline Barc, Jackie Vergote, Pierre Sarradin, Hank F. Kung, Sylvie Chalon, Frédéric Lantier, Université Francois Rabelais [Tours], U930, Institut National de la Santé et de la Recherche Médicale (INSERM), Guiyang Medical University, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Infectiologie Animale et Santé Publique (UR IASP), IFR135, University of Pennsylvania, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), EC [LSHB-CT-2005-512146], Association France Alzheimer, National Institutes of Health [AG-21868], University of Pennsylvania, Philadelphia, USA, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Migration
Subjects: Cancer Research, Pathology, Pyridines, animal diseases, [SDV]Life Sciences [q-bio], Scrapie, Plaque, Amyloid, Iodine Radioisotopes, Mice, 0302 clinical medicine, Microglial activation, PERIPHERAL BENZODIAZEPINE-RECEPTOR, BRAIN, Prion deposit, 0303 health sciences, biology, MULTIPLE-SCLEROSIS, 3. Good health, [SDV] Life Sciences [q-bio], ALZHEIMERS-DISEASE, Oncology, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Chronic inflammatory response, MURINE SCRAPIE, Microglia, medicine.medical_specialty, Prions, Molecular imaging, BINDING-SITES, NEUROINFLAMMATION, 03 medical and health sciences, POSITRON-EMISSION-TOMOGRAPHY, [(125)I]-CLINDE, Translocator protein, medicine, Animals, Radiology, Nuclear Medicine and imaging, CREUTZFELDT-JAKOB, Radionuclide Imaging, 030304 developmental biology, Amyloid fibril, Bridged Bicyclo Compounds, Heterocyclic, nervous system diseases, Mice, Inbred C57BL, Molecular Probes, Translocator protein (18 kDa), biology.protein, Autoradiography, [(125)I]-IMPY, 030217 neurology & neurosurgery
Abstract: International audience; A characteristic of prion diseases which affect both animals and humans is the aggregation of PrP amyloid fibrils in the brain, associated with a chronic inflammatory response dominated by microglial activation. In this study, we hypothesised that specific ligands of the 18-kDa translocator protein (TSPO) would be effective in the evaluation of microglial activation related to PrP(sc) deposits in prion disease. Chronological studies using in vitro autoradiography were carried out with [(3)H]-PK11195 and [(125)I]-IMPY on frozen cerebral sections from scrapie-infected mice and controls. Accumulation of prion deposits was confirmed by histoblot staining with prion protein-specific monoclonal antibody. Ex vivo autoradiographic studies were carried out with [(125)I]-CLINDE and [(125)I]-IMPY at the terminal stage of infection. Chronological studies using in vitro autoradiography showed that PrP(sc) deposits were co-localised with activated microglia as early as 60 days post-inoculation. Progressive levels of PrP(sc) and TSPO staining were successively observed in the hippocampus, cortex and left thalamus of infected mouse brain sections in the course of the disease and were correlated with the signals obtained by histoblot staining. Significant TSPO labelling was also observed ex vivo in the cortex, hippocampus and thalamus of scrapie-infected mice. In parallel, [(125)I]-IMPY showed labelling in the same cerebral regions but with high background staining. These findings indicate the ability of [(125)I]-IMPY and [(125)I]-CLINDE to evaluate prion deposits and microglial activation in vitro and ex vivo in scrapie-infected mice at different stages of the disease.
Published: 2010
Full Text: View/download PDF

40. The bovine prion agent BSE is vertically and horizontally transmissible in sheep flocks

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Christelle Rossignol, Hervé Leroux, Philippe Bernardet, Simmons, H., Jm Torres, Grassi, J., Simon, S., Olivier Andréoletti, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), VLA Weybridge, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ProdInra, Migration, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2009

41. Co-infection par l'ESB et la tremblante inoculées par voie intracérébrale chez les ovins : la tremblante masque l'ESB dans le système nerveux central mais pas dans les tissus lymphoïdes

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Hervé Le Roux, Christelle Rossignol, Philippe Bernardet, Caroline Lacroux, Simmons, H., Grassi, J., Jm Torres, Simon, S., Olivier Andréoletti, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, VLA Weybridge, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), ProdInra, Migration, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2009

42. IMPY and CLINDE as imaging probes candidates for the detection of amyloid deposits and benzodiazepine receptors in prion diseases

Author: Pu Jia, S., Céline Barc, Hugues Leroux, Jackie Vergote, Shirley Chalon, Pierre Sarradin, Mei Ping, K., Frédéric Lantier, Guilloteau, D., Serge Bernard, ProdInra, Migration, Inconnu, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), and Infectiologie Animale et Santé Publique (UR IASP)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

43. Intracerebrally-induced BSE in goats

Author: Patricia Berthon, Isabelle Lantier, Céline Barc, Christelle Rossignol, Leroux, H., Philippe Bernardet, Grassi, J., Olivier Andréoletti, Frédéric Lantier, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

44. BSE transmission to lambs born from infected or contact ewes

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Christelle Rossignol, Leroux, H., Philippe Bernardet, Simmons, H., Grassi, J., Simon, S., Olivier Andréoletti, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Veterinary Laboratories Agency, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ProdInra, Migration, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

45. BSE / Scrapie intracerebrally co-infected sheep : Scrapie hides BSE in the brain, not in lymphoid tissues

Author: Lantier, Frédéric F., Berthon, Patricia P., Céline Barc, Leroux, H., Christelle Rossignol, Philippe Bernardet, Lacroux, Caroline C., Simmons, H., Jacques Grassi, Sunil Simon, Olivier Andréoletti, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Veterinary Laboratories Agency, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

46. Oral transmission of BSE in resistant ARR/ARR sheep: involvement of lymphoid tissues

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Christelle Rossignol, Hugues Leroux, Jacques Grassi, Simmons, H., Jm Torres, Olivier Andréoletti, ProdInra, Migration, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Inconnu, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

47. Genetics of susceptiblility to transmissible spongiform encephalopathies in sheep

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Christelle Rossignol, Philippe Bernardet, Pierre Sarradin, Leroux, H., Serge Bernard, Caroline Lacroux, Grassi, J., Ha Simmons, François Shelcher, Jean Michel Elsen, Olivier Andréoletti, ProdInra, Migration, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), VLA, Station d'Amélioration Génétique des Animaux (SAGA), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2007

48. Genetics susceptiblility of sheep to experimental BSE transmission

Author: Frédéric Lantier, Patricia Berthon, Isabelle Lantier, Céline Barc, Pierre Sarradin, Christelle Rossignol, Philippe Bernardet, Leroux, H., Serge Bernard, Caroline Lacroux, Grassi, J., Ha Simmons, François Shelcher, Jean Michel Elsen, Olivier Andréoletti, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Plateforme d'Infectiologie Expérimentale (PFIE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), VLA, Station d'Amélioration Génétique des Animaux (SAGA), ProdInra, Migration, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2007

49. Natural Scrapie and BSE in genetically resistant sheep

Author: Olivier Andréoletti, Nathalie Morel, Vincent Beringue, Caroline Lacroux, Virginie Rouillon, Céline Barc, Jacques Grassi, Frédéric Lantier, Patricia Berthon, Francois Schelcher, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de Pharmacologie et d'Immunologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Unité de Pathologie Infectieuse et Immunologie [Nouzilly] (PII), ProdInra, Migration, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: [SDV] Life Sciences [q-bio], animal diseases, [SDV]Life Sciences [q-bio], nervous system diseases
Abstract: International audience; Because ARR/ARR genotype sheep were considered to be totally resistant to TSE oralcontamination, they are massively selected in order to protect human food chain from smallruminant BSE risk.A controversial natural scrapie ARR/ARR case was reported in 1994, but genotype of that animalwas never confirmed. Recent identification of (i) atypical abnormal PrP accumulation inasymptomatic animals and (ii) successful transmission of BSE after intracerebral challenge bothraised new concerns about the resistance of ARR/ARR genotype sheep towards natural Priondiseases.However since neither PrPSc nor infectivity was reported in peripheral tissue from the orally orintracerebrally BSE challenged ARR/ARR animals (Bellworthy et al., 2005; Jeffrey et al., 2001).The ‘breeding for resistance’ policy aiming at protecting human food chain was not affected.In a first study, TSE free ARR/ARR and ARQ/ARQ lambs were orally challenged with 5g ofBSE infected sheep brain material. Strikingly, in one challenged ARR/ARR animal, PrPSc wasobserved in spleen at 10 months post challenge. ELISA and WB allowed estimating the totalPrPSc amount in ARR/ARR spleen to be 5 to 10 fold lower than in ARQ/ARQ.In a second study TSE free ARQ/ARQ and ARR/ARR sheep were IC challenged with BSE. Insymptomatic animals from both genotypes, PrPSc was detected in samples from a large panel ofskeletal muscle.Finally the retrospective study of a large scrapie tissue bank allowed us to identify a classicalscrapie case in an ARR/ARR field flock animal.Taken together all those data suggest that ARR/ARR sheep could be lowly susceptible to naturalTSE. It also raises new questions about (i) the pathogenesis and contagiousness of Prion diseasein animals bearing that genotype and (ii) the potential consequence for human food chain.
Published: 2005

50. Multiscale characterization of a lithium/sulfur battery by coupling operando X-ray tomography and spatially-resolved diffraction

Author: Guillaume Tonin, Gavin Vaughan, Renaud Bouchet, Fannie Alloin, Marco Di Michiel, Laura Boutafa, Jean-François Colin, and Céline Barchasz
Subjects: Medicine, Science
Abstract: Abstract Due to its high theoretical specific capacity, the lithium/sulfur battery is one of the most promising candidates for replacing current lithium-ion batteries. In this work, we investigate both chemical and morphological changes in the electrodes during cycling, by coupling operando spatially resolved X-ray diffraction and absorption tomography to characterize Li/S cells under real working conditions. By combining these tools, the state of the active material in the entire cell was correlated with its electrochemical behavior, leading to a deeper understanding of the performance limiting degradation phenomena in Li/S batteries. Highly heterogeneous behavior of lithium stripping/plating was observed in the anode, while the evolution of sulfur distribution in the cathode depth was followed during cycling.
Published: 2017
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

59 results on '"Céline Barc"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources