18 results on '"Fleurot, Isabelle"'
Search Results
2. Evidence of early increased sialylation of airway mucins and defective mucociliary clearance in CFTR-deficient piglets
- Author
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Caballero, Ignacio, Ringot-Destrez, Bélinda, Si-Tahar, Mustapha, Barbry, Pascal, Guillon, Antoine, Lantier, Isabelle, Berri, Mustapha, Chevaleyre, Claire, Fleurot, Isabelle, Barc, Céline, Ramphal, Reuben, Pons, Nicolas, Paquet, Agnès, Lebrigand, Kévin, Baron, Carole, Bähr, Andrea, Klymiuk, Nikolai, Léonard, Renaud, and Robbe-Masselot, Catherine
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- 2021
- Full Text
- View/download PDF
3. Intrinsic alterations in peripheral neutrophils from cystic fibrosis newborn piglets
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Bréa, Déborah, Soler, Laura, Fleurot, Isabelle, Melo, Sandrine, Chevaleyre, Claire, Berri, Mustapha, Labas, Valérie, Teixeira-Gomes, Ana-Paula, Pujo, Julien, Cenac, Nicolas, Bähr, Andrea, Klymiuk, Nikolai, Guillon, Antoine, Si-Tahar, Mustapha, and Caballero, Ignacio
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- 2020
- Full Text
- View/download PDF
4. A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver
- Author
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León-Janampa, Nancy, primary, Caballero-Posadas, Ignacio, additional, Barc, Céline, additional, Darrouzain, François, additional, Moreau, Alain, additional, Guinoiseau, Thibault, additional, Gatault, Philippe, additional, Fleurot, Isabelle, additional, Riou, Mickaël, additional, Pinard, Anne, additional, Pezant, Jérémy, additional, Rossignol, Christelle, additional, Gaudy-Graffin, Catherine, additional, Brand, Denys, additional, and Marlet, Julien, additional
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- 2023
- Full Text
- View/download PDF
5. Exploring type I interferon pathway: virulent vs. attenuated strain of African swine fever virus revealing a novel function carried by MGF505-4R.
- Author
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Dupré, Juliette, le Le Dimna, Mireil, Hutet, Evelyne, Dujardin, Pascal, Fablet, Aurore, Leroy, Aurélien, Fleurot, Isabelle, Karadjian, Grégory, Roesch, Ferdinand, Caballero, Ignacio, Bourry, Olivier, Vitour, Damien, Le Potier, Marie-Frédé rique, and Caignard, Grégory
- Subjects
AFRICAN swine fever virus ,TYPE I interferons ,ACTINOBACILLUS pleuropneumoniae ,GENE expression ,ALVEOLAR macrophages ,VIRAL genes - Abstract
African swine fever virus represents a significant reemerging threat to livestock populations, as its incidence and geographic distribution have surged over the past decade in Europe, Asia, and Caribbean, resulting in substantial socio-economic burdens and adverse effects on animal health and welfare. In a previous report, we described the protective properties of our newly thermo-attenuated strain (ASFV- 989) in pigs against an experimental infection of its parental Georgia 2007/1 virulent strain. In this new study, our objective was to characterize the molecular mechanisms underlying the attenuation of ASFV-989. We first compared the activation of type I interferon pathway in response to ASFV-989 and Georgia 2007/1 infections, employing both in vivo and in vitro models. Expression of IFN-a was significantly increased in porcine alveolar macrophages infected with ASFV-989 while pigs infectedwith Georgia 2007/1 showed higher IFN-a than those infected by ASFV-989. We also used a medium-throughput transcriptomic approach to study the expression of viral genes by both strains, and identified several patterns of gene expression. Subsequently, we investigated whether proteins encoded by the eight genes deleted in ASFV-989 contribute to the modulation of the type I interferon signaling pathway. Using different strategies, we showed that MGF505-4R interfered with the induction of IFN-α/β pathway, likely through interaction with TRAF3. Altogether, our data reveal key differences between ASFV-989 and Georgia 2007/ 1 in their ability to control IFN-α/β signaling and provide molecular mechanisms underlying the role of MGF505-4R as a virulence factor. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
6. Milk maturation temperature and time are key technological parameters to limit staphylococcal enterotoxin production during uncooked semi-hard cheese manufacture
- Author
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Duquenne, Manon, Derzelle, Sylviane, Fleurot, Isabelle, Aigle, Marina, Darrigo, Claire, Hennekinne, Jacques-Antoine, Mutel, Isabelle, Bouix, Marielle, Deperrois-Lafarge, Véronique, and Delacroix-Buchet, Agnès
- Published
- 2016
- Full Text
- View/download PDF
7. TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium
- Author
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Fleurot, Isabelle, López-Gálvez, Raquel, Barbry, Pascal, Guillon, Antoine, Si-Tahar, Mustapha, Bähr, Andrea, Klymiuk, Nikolai, Sirard, Jean-Claude, and Caballero, Ignacio
- Published
- 2022
- Full Text
- View/download PDF
8. Airway administration of flagellin regulates the inflammatory response to Pseudomonas aeruginosa
- Author
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López-Gálvez, Raquel, Fleurot, Isabelle, Chamero, Pablo, Trapp, Sascha, Olivier, Michel, Chevaleyre, Claire, Barc, Céline, Riou, Mickael, Rossignol, Christelle, Guillon, Antoine, Si-Tahar, Mustapha, May, Tobias, Barbry, Pascal, Bähr, Andrea, Klymiuk, Nikolai, Sirard, Jean-Claude, Caballero, Ignacio, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 Médecine Intensive et Réanimation [Tours], Inscreenex GmbH, Institut de pharmacologie moléculaire et cellulaire (IPMC), 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), Ludwig Maximilian University [Munich] (LMU), Gene Center and Center for Innovation Medical Models (CiMM), Ludwig-Maximilians University [Munich] (LMU), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Chanteloup, Nathalie Katy, Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur], Université de Tours (UT), 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), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Ludwig Maximilians University of Munich, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-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
[SDV.IMM] Life Sciences [q-bio]/Immunology ,Swine ,[SDV]Life Sciences [q-bio] ,Epithelial Cells ,flagellin ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Immunity, Innate ,cystic fibrosis ,Asthma and Airway Inflammation ,inflammation ,Pseudomonas aeruginosa ,Animals ,bacteria ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Pseudomonas Infections ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Lung ,TLR5 ,Original Research ,Signal Transduction - Abstract
International audience; 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 to Pseudomonas aeruginosa infection. Moreover, in vivo administration of flagellin decreased the severity of P. aeruginosa-induced pneumonia. Then we confirmed these beneficial effects of flagellin in a pathological model of CF by using ex vivo precision-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
- Full Text
- View/download PDF
9. TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium
- Author
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Fleurot, Isabelle, primary, López-Gálvez, Raquel, additional, Barbry, Pascal, additional, Guillon, Antoine, additional, Si-Tahar, Mustapha, additional, Bähr, Andrea, additional, Klymiuk, Nikolai, additional, Sirard, Jean-Claude, additional, and Caballero, Ignacio, additional
- Published
- 2021
- Full Text
- View/download PDF
10. Flagellin pre-stimulation modulates the immune response to pathogens in pig airway epithelial cells
- Author
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Fleurot, Isabelle, Melo, Sandrine, Olivier, Michel, Chevaleyre, Claire, Carnoy, Christophe, Sirard, Jean Claude, Caballero, Ignacio, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Université de Lille, and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
- Subjects
[SDV.IMM]Life Sciences [q-bio]/Immunology ,ComputingMilieux_MISCELLANEOUS - Abstract
Session : Posters; National audience
- Published
- 2018
11. Comparison of pathogenicity and intestinal immunity outcomes in infected pigs with French InDel and US non-InDel strains of porcine epidemic diarrhea virus
- Author
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Gallien, Sarah, Rossignol, Christelle, Fleurot, Isabelle, Chevaleyre, Claire, Bernard, C., Bigault, Lionel, Melo, Sandrina, Moro, Angélique, Lediguerher, Gérald, Paboeuf, Frédéric, Rose, Nicolas, Grasland, Béatrice, Berri, Mustapha, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université Bretagne Loire (COMUE) (UBL), and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
- Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2018
12. Visualization of the role of host heme on the virulence of the heme auxotroph Streptococcus agalactiae
- Author
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Joubert, Laétitia, Dagieu, Jean-Baptiste, Fernandez, Annabelle, Bobillot, Aurelie, Borezée-Durant, Elise, Fleurot, Isabelle, Gruss, Alexandra, Lechardeur, Delphine, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Fromageries Bel, Infectiologie Animale et Santé Publique - IASP (Nouzilly, France), Institut National de la Recherche Agronomique (INRA), HemeStockExchange ANR-12-BSV3-0022-01 project by the French 'Agence Nationale de la Recherche' - French National Research Agency ANR-11-IDEX-0003-02, 'ALIAS' project., Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), ANR-12-BSV3-0022,HEMESTOCKEXCHANGE,Hème et porphyrine chez des bactéries modèle: des fonctions aux mécanismes(2012), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
- Subjects
auxotrophie ,Virulence ,infection bactérienne ,Intracellular Space ,auxotrophy ,toxicity ,virulence factor ,Aerobiosis ,Article ,Mice ,ferroprotoporphyrin ,facteur de virulence ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Genes, Bacterial ,Streptococcal Infections ,Animals ,toxicité ,streptococcus agalactiae ,heme - Abstract
International audience; Heme is essential for several cellular key functions but is also toxic. Whereas most bacterial pathogens utilize heme as a metabolic cofactor and iron source, the impact of host heme during bacterial infection remains elusive. The opportunist pathogen Streptococcus agalactiae does not synthesize heme but still uses it to activate a respiration metabolism. Concomitantly, heme toxicity is mainly controlled by the HrtBA efflux transporter. Here we investigate how S. agalactiae manages heme toxicity versus benefits in the living host. Using bioluminescent bacteria and heme-responsive reporters for in vivo imaging, we show that the capacity of S. agalactiae to overcome heme toxicity is required for successful infection, particularly in blood-rich organs. Host heme is simultaneously required, as visualized by a generalized infection defect of a respiration-negative mutant. In S. agalactiae, HrtBA expression responds to an intracellular heme signal via activation of the two-component system HssRS. A hssRS promoter-driven intracellular luminescent heme sensor was designed to identify host compartments that supply S. agalactiae with heme. S. agalactiae acquires heme in heart, kidneys, and liver, but not in the brain. We conclude that S. agalactiae response to heme is organ-dependent, and its efflux may be particularly relevant in late stages of infection.
- Published
- 2017
- Full Text
- View/download PDF
13. Tool for quantification of staphylococcal enterotoxin gene expression in cheese
- Author
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Duquenne, Manon, Fleurot, Isabelle, Aigle, Marina, Darrigo, Claire, Borezee-Durant, Elise, Derzelle, Sylviane, Bouix, Marielle, Deperrois-Lafarge, Veronique, and Delacroix-Buchet, Agnes
- Subjects
Cheese -- Properties ,Enterotoxins -- Research ,Gene expression -- Analysis ,Polymerase chain reaction -- Usage ,Staphylococcus -- Genetic aspects ,Staphylococcus -- Physiological aspects ,Biological sciences - Abstract
An efficient procedure to recover total RNA from cheese was developed and a robust strategy to study gene expression by reverse transcription-quantitative PCR was applied in order to study enterotoxin gene expression during cheese manufacture. The developed method yielded pure preparations of undegraded RNA suitable for RT-qPCR and presents an easily transferable set of tools to study gene expression of minor species in a complex ecosystem.
- Published
- 2010
14. The preconceptional environment affects the implantation process in a murine model of spontaneous abortion
- Author
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Chaouat, G., Coqué, Nathalie, Hennuy, B., Dubanchet, S., Rodde, Nathalie, Fleurot, Isabelle, Ledée, N., Sandra, Olivier, INSERM U782, Hôpital Antoine Béclère, Mathématiques et Informatique Appliquées (MIA-Paris), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, EMBIC, Lab Tumor Development, Centre Hospitalier Universitaire de Liège, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
- Subjects
[SDV]Life Sciences [q-bio] ,IMPLANTATION FOETALE - Abstract
absent
- Published
- 2008
15. Cytokine expression at interface : a longitudinal micro array
- Author
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Chaouat, G., Coqué, Nathalie, Hennuy, B., Dubanchet, S., Fleurot, Isabelle, Rodde, Nathalie, Ledée-Bataille, N., Sandra, Olivier, U782, Institut National de la Santé et de la Recherche Médicale (INSERM), Mathématiques et Informatique Appliquées (MIA-Paris), AgroParisTech-Institut National de la Recherche Agronomique (INRA), EMBIC, Tumor and Developement Laboratory, Université de Liège, Station de physiologie animale, Institut National de la Recherche Agronomique (INRA), Unité 782, UR 0888 Bactéries Lactiques et Pathogènes Opportunistes, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-Bactéries Lactiques et Pathogènes Opportunistes (UBLO), and Biologie du Développement et Reproduction (BDR)
- Subjects
reproduction ,microarray ,cytokineexpression ,interface ,network ,méthode ,CYTOKINE ,biopuce ,[SDV]Life Sciences [q-bio] ,réseau - Abstract
Main Session 3: Immuno-Endocrine Interactions in Reproduction.; absent
- Published
- 2008
- Full Text
- View/download PDF
16. Following Pathogen Development and Gene Expression in a Food Ecosystem: the Case of a Staphylococcus aureus Isolate in Cheese
- Author
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Fleurot, Isabelle, primary, Aigle, Marina, additional, Fleurot, Renaud, additional, Darrigo, Claire, additional, Hennekinne, Jacques-Antoine, additional, Gruss, Alexandra, additional, Borezée-Durant, Elise, additional, and Delacroix-Buchet, Agnès, additional
- Published
- 2014
- Full Text
- View/download PDF
17. Following Pathogen Development and Gene Expression in a Food Ecosystem: the Case of a Staphylococcus aureus Isolate in Cheese
- Author
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Jacques-Antoine Hennekinne, Alexandra Gruss, Renaud Fleurot, Elise Borezée-Durant, Claire Darrigo, Marina Aigle, A. Delacroix-Buchet, Isabelle Fleurot, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Unité Staphylocoques, Bacillus, Clostridies, Lait (Unité SBCL), Laboratoire de sécurité des aliments de Maisons-Alfort, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Ile-de-France, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), and Fleurot, Isabelle
- Subjects
Staphylococcus aureus ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,milk ,bacteria ,United-States ,identification ,dairy-product ,in-situ hybridization ,microstructure ,foodborne illness ,enterotoxin production ,lactococcus-lactis ,Ingénierie des aliments ,Food Contamination ,medicine.disease_cause ,Staphylococcal infections ,Applied Microbiology and Biotechnology ,Microbiology ,Enterotoxins ,Bacterial Proteins ,Cheese ,[SDV.IDA]Life Sciences [q-bio]/Food engineering ,medicine ,Food microbiology ,Food engineering ,Humans ,Pathogen ,Ecosystem ,2. Zero hunger ,Food poisoning ,Ecology ,biology ,Lactococcus lactis ,Staphylococcal Infections ,medicine.disease ,biology.organism_classification ,Food Microbiology ,Bacteria ,Food Science ,Biotechnology ,Food contaminant ,Autre (Sciences du Vivant) - Abstract
Human intoxication or infection due to bacterial food contamination constitutes an economic challenge and a public health problem. Information on the in situ distribution and expression of pathogens responsible for this risk is to date lacking, largely because of technical bottlenecks in detecting signals from minority bacterial populations within a complex microbial and physicochemical ecosystem. We simulated the contamination of a real high-risk cheese with a natural food isolate of Staphylococcus aureus , an enterotoxin-producing pathogen responsible for food poisoning. To overcome the problem of a detection limit in a solid matrix, we chose to work with a fluorescent reporter (superfolder green fluorescent protein) that would allow spatiotemporal monitoring of S. aureus populations and targeted gene expression. The combination of complementary techniques revealed that S. aureus localizes preferentially on the cheese surface during ripening. Immunochemistry and confocal laser scanning microscopy enabled us to visualize, in a single image, dairy bacteria and pathogen populations, virulence gene expression, and the toxin produced. This procedure is readily applicable to other genes of interest, other bacteria, and different types of food matrices.
- Published
- 2014
- Full Text
- View/download PDF
18. Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa .
- Author
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López-Gálvez R, Fleurot I, Chamero P, Trapp S, Olivier M, Chevaleyre C, Barc C, Riou M, Rossignol C, Guillon A, Si-Tahar M, May T, Barbry P, Bähr A, Klymiuk N, Sirard JC, and Caballero I
- Subjects
- Animals, Epithelial Cells drug effects, Epithelial Cells metabolism, Epithelial Cells microbiology, Flagellin immunology, Flagellin metabolism, Immunity, Innate drug effects, Lung immunology, Lung microbiology, Lung pathology, Pseudomonas Infections immunology, Pseudomonas aeruginosa immunology, Signal Transduction drug effects, Swine, Flagellin pharmacology, Inflammation drug therapy, Pseudomonas Infections drug therapy, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa pathogenicity
- 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 to Pseudomonas aeruginosa infection. Moreover, in vivo administration of flagellin decreased the severity of P. aeruginosa -induced pneumonia. Then we confirmed these beneficial effects of flagellin in a pathological model of CF by using ex vivo precision-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
- Full Text
- View/download PDF
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