Thibaut Larcher - Academia.edu (original) (raw)

Papers by Thibaut Larcher

Research paper thumbnail of Sécrétion inductible d''EPO par le muscle transduit grâce à un AAVr

Une regulation pharmacologique fine de l''expression du transgene est indispensable pour ... more Une regulation pharmacologique fine de l''expression du transgene est indispensable pour certaines applications de therapie genique. L''injection intramusculaire a des macaques cynomolgus, de virus recombinant adeno-associe (AAVr) de differents serotypes codant pour l''eythropoietine (EPO) sous controle du systeme de regulation aux tetracyclines (systeme Tet-on), est suivie d''une expression inductible mais transitoire du transgene. Cette synthese proteique massive et ectopique peut entrainer une anemie auto-immune reversible.

Research paper thumbnail of Direct and indirect effects of multiple environmental stressors on fish health in human-altered rivers

Science of The Total Environment, 2020

Freshwater fish face multiple challenges in human-altered rivers such as trace metal contaminatio... more Freshwater fish face multiple challenges in human-altered rivers such as trace metal contamination, temperature increase and parasitism. These multiple stressors could have unexpected interactive effects on fish health due to shared physiological pathways, but few studies investigated this question in wild fish populations. In this study, we compared 16 populations of gudgeon (Gobio occitaniae) distributed along perturbation gradients in humanaltered rivers in the South of France. We tested the effects of single and combined stressors (i.e., metal contamination, temperature, parasitism) on key traits linked to fish health across different biological levels using a Structural Equation Modelling approach. Parasitism and temperature alone had limited deleterious effects on fish health. In contrast, fish living in metal-contaminated sites had higher metal bioaccumulation and higher levels of cellular damage in the liver through the induction of an inflammatory response. In addition, temperature and contamination had interactive negative effects on growth. These results suggest that trace metal contamination has deleterious effects on fish health at environmentally realistic concentrations and that temperature can modulate the effects of trace metals on fish growth. With this study, we hope to encourage integrative approaches in realistic field conditions to better predict the effects of natural and anthropogenic stressors on aquatic organisms.

Research paper thumbnail of MRI texture analysis of GRMD dogs using orthogonal moments: A preliminary study

IRBM, 2015

Magnetic resonance image texture analysis (MRI-TA) has been already demonstrated as a powerful to... more Magnetic resonance image texture analysis (MRI-TA) has been already demonstrated as a powerful tool to extract image information better than visual examination of grey levels. Human muscular dystrophy is a disease of which diagnosis is rather easy but it remains a lack of atraumatic methods for its follow-up as well as for the management of treatments presently in progress. MRI appears to be a potential tool for disease follow-up and treatment monitoring. The present study is part of the European project MYO-MRI (http :/ /myo-mri .eu/) aimed at improving diagnosis and understanding of muscle pathology. This paper focuses on the use of Legendre and Zernike moment-based texture analysis of MRI T2-weighted images to follow from 2 to 14 months 5 healthy and 5 Golden Retriever Muscular Dystrophy Dogs (GRMD), acknowledged to be the most accurate animal model available for human Duchenne Muscular Dystrophy. Regions-Of-Interest (ROIs) were characterized by moments and the features so extracted were analyzed by Principal Component Analysis and classified by means of Support Vector Machine. The preliminary results show relevant discriminations between dogs populations in reference to disease status and evolution.

Research paper thumbnail of Efficacy of epicutaneous immunotherapy (EPIT) in a new model of peanut-induced eosinophilic esophagitis (EoE) and allergic enterpathy (AE)

Research paper thumbnail of Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice

Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associat... more Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm 2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm 2 , p,0.05), mRNA expression of Th2 cytokines in tissue-eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05)-, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

Research paper thumbnail of Effect of experimental infection with Haemonchus contortus on parasitological and local cellular responses in resistant and susceptible young Creole goats

BioMed research international, 2013

This study was carried out to evaluate the relationships of cellular changes in the abomasal muco... more This study was carried out to evaluate the relationships of cellular changes in the abomasal mucosa and parasitological parameters, by comparing resistant and susceptible young Creole goats (kids) after experimental infection with Haemonchus contortus. The kids were infected over 2 periods (challenges 1 and 2) of 7 and 6 weeks, respectively. Fecal egg count (FEC), blood eosinophilia, packed cell volume (PCV), and body weight were weekly monitored. At the end of both challenges a subgroup of kids was slaughtered for nematode burden measurements and analysis of inflammatory cell infiltration in the abomasal mucosa. The average daily gain was higher in resistant kids after both challenges. Blood eosinophilia and FEC were higher in susceptible kids after both challenges. The number of immature worms and the means of female length were lower after challenge 2 whatever the genetic status. No differences were observed in the eosinophil and mononuclear cell infiltration between challenges 1 and 2 and resistant and susceptible kids. Globule leukocyte infiltration was found higher after the challenge 1 in resistant kids. This effect of the genetic status on globule leukocytes counts but not on the other inflammatory cell highlights the need for further study on the functional activity of these cell populations.

Research paper thumbnail of Omicron BA.5 infects human brain organoids and is neuroinvasive and lethal in K18-hACE2 mice

A frequently repeated premise is that viruses evolve to become less pathogenic. This appears also... more A frequently repeated premise is that viruses evolve to become less pathogenic. This appears also to be true for SARS-CoV-2, although the increased level of immunity in human populations makes it difficult to distinguish between reduced intrinsic pathogenicity and increasing protective immunity. The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described and appears to be due to reduced utilization of TMPRRS2. That this reduced pathogenicity remains true for omicron BA.5 was recently reported. In sharp contrast, we show that a BA.5 isolate was significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, with BA.5 infection showing increased neurovirulence, encephalitis and mortality, similar to that seen for an original strain isolate. BA.5 also infected human cortical brain organoids to a greater extent than a BA.1 and original strain isolate. Neurons were the target of infection, with increasing evidence of neuron infection in C...

Research paper thumbnail of L’herpèsvirus de la maladie de Marek induit une atrophie des organes lymphoïdes primaires durant l’infection précoce, associée à un accroissement d’apoptose, à une inhibition de la prolifération cellulaire et à une forte lymphopénie B

Le Centre pour la Communication Scientifique Directe - HAL - Université Francois Rabelais - Tours, Mar 22, 2018

National audienc

Research paper thumbnail of Phenotypic characterization and myogenic potential of human MuStem cells, candidates for therapy of Duchenne Muscular Dystrophy

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Oct 25, 2012

Research paper thumbnail of Establishment of a culture model for the prolonged maintenance of chicken feather follicles structure in vitro

PLOS ONE

Protocols allowing the in vitro culture of human hair follicles in a serum free-medium up to 9 da... more Protocols allowing the in vitro culture of human hair follicles in a serum free-medium up to 9 days were developed 30 years ago. By using similar protocols, we achieved the prolonged maintenance in vitro of juvenile feather follicles (FF) microdissected from young chickens. Histology showed a preservation of the FF up to 7 days as well as feather morphology compatible with growth and/or differentiation. The integrity of the FF wall epithelium was confirmed by transmission electron microscopy at Day 5 and 7 of culture. A slight elongation of the feathers was detected up to 5 days for 75% of the examined feathers. By immunochemistry, we demonstrated the maintenance of expression and localization of two structural proteins: scaffoldin and fibronectin. Gene expression (assessed by qRT-PCR) of NCAM, LCAM, Wnt6, Notch1, and BMP4 was not altered. In contrast, Shh and HBS1 expression collapsed, DKK3 increased, and KRT14 transiently increased upon cultivation. This indicates that cultivation...

Research paper thumbnail of Développement d'un modèle pré-clinique à l'infection du Chikungunya

Le Centre pour la Communication Scientifique Directe - HAL - CEA - Commissariat à l’énergie atomique, Nov 24, 2010

National audienceContexte, objectifs: La compréhension de la maladie à Chikungunya qui se caracté... more National audienceContexte, objectifs: La compréhension de la maladie à Chikungunya qui se caractérise par l'induction de douleur articulaire et musculaire chronique à long terme. Le laboratoire a développé un modèle d'infection expérimentale par le virus du Chikungunya chez le macaque cynomolgus afin d'explorer celle-ci à moyen et long terme. Résultats: Ce modèle reproduit lors de l'infection aigüe les signes cliniques et un profil d'évolution des paramètres virologiques et immunologiques proches de l'infection humaine. Nous avons identifié les sites de réplication virale et mis en évidence la persitance du virus dans les tissus ce qui permet pour la première fois de donner un début d'explication à la pathologie à long terme. Nous avons utilisé ce modèle pour évaluer une méthode prophylactique proposé lors de l'épidémie de la Réunion en 2006. Conclusion: Associé aux essais sur des modèles murins représentatifs de l'infection en phase aiguë, l'utilisation des primates non-humain est indispensable pour valider en préclinique des stratégies vaccinales ou prophylactiques s'appliquant à la période chronique de l'infection

Research paper thumbnail of Preclinical Evaluation of a Novel Epicutaneous Vaccine against Respiratory Syncytial Virus

International audienceIn order to be able to put an RSV vaccine onto the market, new vaccination ... more International audienceIn order to be able to put an RSV vaccine onto the market, new vaccination strategies combining scientific and technical innovation need to be explored. In the present project, we describe the development and the non-clinical evaluation of an original epicutaneous RSV vaccine that combines two patented technologies: Viaskin® epicutaneous patches developed by DBV Technologies as a delivery platform, and RSV N-nanorings fused to the F epitope targeted by palivizumab (N-FsII) developed by the French National Institute for Agronomical Research (INRA) as a subunit antigen. We have demonstrated that Viaskin® loaded with a formulation containing N-FsII antigen (Viaskin®- N-FsII) is highly immunogenic in mice and promote a Th1/Th17 oriented immune response. More importantly, Viaskin®-N-FsII epicutaneous vaccine confers a high level of protection against viral replication upon RSV challenge in mice, without exacerbating clinical symptoms. In swine, which provides the be...

Research paper thumbnail of La longueur de la tige de la neuraminidase d'un virus influenza aviaire H7N1 produit des effets opposés chez le poulet et le canard

National audienceOne of the host-range determinants that favor the multiplication of influenza vi... more National audienceOne of the host-range determinants that favor the multiplication of influenza viruses in domestic poultry is the length of the neuraminidase (NA) stalk: a deletion of about 20 amino acids in the NA-stalk is frequently detected upon transmission of influenza A viruses from waterfowl to domestic poultry and was recently associated with increased virulence in chicken. Whether this modification has any effect in ducks is currently unknown. Using reverse genetics, a recombinant virus derived from a turkey H7N1 influenza virus isolate with a short-stalk neuraminidase, A/turkey/Italy/977/1999, and an NA stalk insertion variant (insNA) were produced. Four-week-old chickens that were inoculated via the intratracheal and oral routes with the insNA virus showed a better survival and a lower oro-pharyngeal excretion than those inoculated with the wt-virus. The two viruses did not differ as regards viral loads in the lungs, kidneys and caeca, but the short-stalk NA virus induced...

Research paper thumbnail of Dystrophin expression after locoregional injection of rAAV8-U7SnRNA vectors in the forelimb of GRMD dogs

Research paper thumbnail of Mode of Delivery and Cell Tropism Versus Immunotoxicity of Recombinant AAV in Nonhuman Primate

Abstracts 8th Annual Meeting French Society of Cell and Gene Therapy, 21–23 June 2009, Faculté de... more Abstracts 8th Annual Meeting French Society of Cell and Gene Therapy, 21–23 June 2009, Faculté de Médecine de la Pitié-Salpêtrière Paris, France SFTCG 2009 Invited PresentationsInternational audienc

Research paper thumbnail of Assessment of TRPC1 and TRPC3 as Potential Therapeutic Targets for DMD Treatment in Complement to rAAV-microDystrophin Gene Therapy

Le Centre pour la Communication Scientifique Directe - HAL - memSIC, Apr 9, 2021

International audienc

Research paper thumbnail of Exploration of muscle from GRMD dogs transplanted with MuStem cells using "omics" approaches

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Oct 14, 2013

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Research paper thumbnail of Temperature variations during incubation and postnatal period affect performance, metabolism, health and gene expression in the blood of fast-growing chickens

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Sep 17, 2018

Research paper thumbnail of An aberrant age of liver DNA methylation is associated with cloning-induced pathologies

Le Centre pour la Communication Scientifique Directe - HAL - Université de Nantes, Nov 16, 2015

National audienceIt is postulated that the developmental defects frequently observed in somalie c... more National audienceIt is postulated that the developmental defects frequently observed in somalie clones arise from inappropriate reprogramming of the donor epigenome by the oocyte. We used cattle clones as a model to investigate the long­ lerm effects of nuclear reprogramming on both DNA methylation and the phenotype of a differentiated organ, the liver. Pathological perinatal clones and apparently normal adult clones, both produced within one decade, were studied, together with age-matched controls. We identified differentially methylated regions (DMRs) in gene promoters displaying variations according to age and to the clone status of the animals. Strikingly, whereas adult clones did not differ significantly from adult controls, perinatal clones showed a demethylation at DMRs inconsistent with their chronological age. Pathological features were found in the liver of perinatal clones only, with histological lesions and modifications to both histomorphometrical and metabolic parameters. The integration of DMRs with phenotypic datasets led to the identification of epigenetic alterations correlated to phenotypic abnormalities in perinatal clones. Genes important to the antioxidant response and energy metabolism were targeted by these alterations. For at !east one DMR, the aberrant methylation profile in perinatal clones was associated with altered gene expression. The liver defects encountered in pathological perinatal clones could be associated to the aberrant age of DNA methylation, at genes indicating potential deficits in oxidative metabolism. We propose that epigenetic ageing is an adaptation to the excessive oxidative stress induced by reprogramming that the pathological clones were not able to counteract during subsequent developmental stages

Research paper thumbnail of Effects of post-hatch fast of chick on digestive tract development and growth performance according to diet and rearing environmental conditions

In commercial conditions, chicks underwent a post-hatch fast (PHF) between 24 and 72h, and about ... more In commercial conditions, chicks underwent a post-hatch fast (PHF) between 24 and 72h, and about 24h when hatchery and farm are in the same region. Effects on digestive tract development (DTD) and animal growth are controversial due to several factors such as definition of bird age (from hatching in most studies, or from farm arrival), animal genetics, or dietary and environmental conditions (DEC). Here, the effect of PHF was studied on body weight (BW) and DTD of Ross PM3, during a first experiment (48h fast), with age of birds determined as the age at farm arrival with access to feed and water. To study the effect of DEC, birds were reared either in optimal DEC, or damaged DEC (low quality diet and/or low quality rearing environment) in a 2x2x2 factorial design (6 pens/treatment ; 54 birds/pen of 2.3 m2 of useful area). In a second experiment, the effect of a shorter PHF (24h) was studied on chick BW and DTD. In the first study, PHF showed effects on DTD, BW and animal health, dif...

Research paper thumbnail of Sécrétion inductible d''EPO par le muscle transduit grâce à un AAVr

Une regulation pharmacologique fine de l''expression du transgene est indispensable pour ... more Une regulation pharmacologique fine de l''expression du transgene est indispensable pour certaines applications de therapie genique. L''injection intramusculaire a des macaques cynomolgus, de virus recombinant adeno-associe (AAVr) de differents serotypes codant pour l''eythropoietine (EPO) sous controle du systeme de regulation aux tetracyclines (systeme Tet-on), est suivie d''une expression inductible mais transitoire du transgene. Cette synthese proteique massive et ectopique peut entrainer une anemie auto-immune reversible.

Research paper thumbnail of Direct and indirect effects of multiple environmental stressors on fish health in human-altered rivers

Science of The Total Environment, 2020

Freshwater fish face multiple challenges in human-altered rivers such as trace metal contaminatio... more Freshwater fish face multiple challenges in human-altered rivers such as trace metal contamination, temperature increase and parasitism. These multiple stressors could have unexpected interactive effects on fish health due to shared physiological pathways, but few studies investigated this question in wild fish populations. In this study, we compared 16 populations of gudgeon (Gobio occitaniae) distributed along perturbation gradients in humanaltered rivers in the South of France. We tested the effects of single and combined stressors (i.e., metal contamination, temperature, parasitism) on key traits linked to fish health across different biological levels using a Structural Equation Modelling approach. Parasitism and temperature alone had limited deleterious effects on fish health. In contrast, fish living in metal-contaminated sites had higher metal bioaccumulation and higher levels of cellular damage in the liver through the induction of an inflammatory response. In addition, temperature and contamination had interactive negative effects on growth. These results suggest that trace metal contamination has deleterious effects on fish health at environmentally realistic concentrations and that temperature can modulate the effects of trace metals on fish growth. With this study, we hope to encourage integrative approaches in realistic field conditions to better predict the effects of natural and anthropogenic stressors on aquatic organisms.

Research paper thumbnail of MRI texture analysis of GRMD dogs using orthogonal moments: A preliminary study

IRBM, 2015

Magnetic resonance image texture analysis (MRI-TA) has been already demonstrated as a powerful to... more Magnetic resonance image texture analysis (MRI-TA) has been already demonstrated as a powerful tool to extract image information better than visual examination of grey levels. Human muscular dystrophy is a disease of which diagnosis is rather easy but it remains a lack of atraumatic methods for its follow-up as well as for the management of treatments presently in progress. MRI appears to be a potential tool for disease follow-up and treatment monitoring. The present study is part of the European project MYO-MRI (http :/ /myo-mri .eu/) aimed at improving diagnosis and understanding of muscle pathology. This paper focuses on the use of Legendre and Zernike moment-based texture analysis of MRI T2-weighted images to follow from 2 to 14 months 5 healthy and 5 Golden Retriever Muscular Dystrophy Dogs (GRMD), acknowledged to be the most accurate animal model available for human Duchenne Muscular Dystrophy. Regions-Of-Interest (ROIs) were characterized by moments and the features so extracted were analyzed by Principal Component Analysis and classified by means of Support Vector Machine. The preliminary results show relevant discriminations between dogs populations in reference to disease status and evolution.

Research paper thumbnail of Efficacy of epicutaneous immunotherapy (EPIT) in a new model of peanut-induced eosinophilic esophagitis (EoE) and allergic enterpathy (AE)

Research paper thumbnail of Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice

Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associat... more Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm 2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm 2 , p,0.05), mRNA expression of Th2 cytokines in tissue-eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05)-, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

Research paper thumbnail of Effect of experimental infection with Haemonchus contortus on parasitological and local cellular responses in resistant and susceptible young Creole goats

BioMed research international, 2013

This study was carried out to evaluate the relationships of cellular changes in the abomasal muco... more This study was carried out to evaluate the relationships of cellular changes in the abomasal mucosa and parasitological parameters, by comparing resistant and susceptible young Creole goats (kids) after experimental infection with Haemonchus contortus. The kids were infected over 2 periods (challenges 1 and 2) of 7 and 6 weeks, respectively. Fecal egg count (FEC), blood eosinophilia, packed cell volume (PCV), and body weight were weekly monitored. At the end of both challenges a subgroup of kids was slaughtered for nematode burden measurements and analysis of inflammatory cell infiltration in the abomasal mucosa. The average daily gain was higher in resistant kids after both challenges. Blood eosinophilia and FEC were higher in susceptible kids after both challenges. The number of immature worms and the means of female length were lower after challenge 2 whatever the genetic status. No differences were observed in the eosinophil and mononuclear cell infiltration between challenges 1 and 2 and resistant and susceptible kids. Globule leukocyte infiltration was found higher after the challenge 1 in resistant kids. This effect of the genetic status on globule leukocytes counts but not on the other inflammatory cell highlights the need for further study on the functional activity of these cell populations.

Research paper thumbnail of Omicron BA.5 infects human brain organoids and is neuroinvasive and lethal in K18-hACE2 mice

A frequently repeated premise is that viruses evolve to become less pathogenic. This appears also... more A frequently repeated premise is that viruses evolve to become less pathogenic. This appears also to be true for SARS-CoV-2, although the increased level of immunity in human populations makes it difficult to distinguish between reduced intrinsic pathogenicity and increasing protective immunity. The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described and appears to be due to reduced utilization of TMPRRS2. That this reduced pathogenicity remains true for omicron BA.5 was recently reported. In sharp contrast, we show that a BA.5 isolate was significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, with BA.5 infection showing increased neurovirulence, encephalitis and mortality, similar to that seen for an original strain isolate. BA.5 also infected human cortical brain organoids to a greater extent than a BA.1 and original strain isolate. Neurons were the target of infection, with increasing evidence of neuron infection in C...

Research paper thumbnail of L’herpèsvirus de la maladie de Marek induit une atrophie des organes lymphoïdes primaires durant l’infection précoce, associée à un accroissement d’apoptose, à une inhibition de la prolifération cellulaire et à une forte lymphopénie B

Le Centre pour la Communication Scientifique Directe - HAL - Université Francois Rabelais - Tours, Mar 22, 2018

National audienc

Research paper thumbnail of Phenotypic characterization and myogenic potential of human MuStem cells, candidates for therapy of Duchenne Muscular Dystrophy

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Oct 25, 2012

Research paper thumbnail of Establishment of a culture model for the prolonged maintenance of chicken feather follicles structure in vitro

PLOS ONE

Protocols allowing the in vitro culture of human hair follicles in a serum free-medium up to 9 da... more Protocols allowing the in vitro culture of human hair follicles in a serum free-medium up to 9 days were developed 30 years ago. By using similar protocols, we achieved the prolonged maintenance in vitro of juvenile feather follicles (FF) microdissected from young chickens. Histology showed a preservation of the FF up to 7 days as well as feather morphology compatible with growth and/or differentiation. The integrity of the FF wall epithelium was confirmed by transmission electron microscopy at Day 5 and 7 of culture. A slight elongation of the feathers was detected up to 5 days for 75% of the examined feathers. By immunochemistry, we demonstrated the maintenance of expression and localization of two structural proteins: scaffoldin and fibronectin. Gene expression (assessed by qRT-PCR) of NCAM, LCAM, Wnt6, Notch1, and BMP4 was not altered. In contrast, Shh and HBS1 expression collapsed, DKK3 increased, and KRT14 transiently increased upon cultivation. This indicates that cultivation...

Research paper thumbnail of Développement d'un modèle pré-clinique à l'infection du Chikungunya

Le Centre pour la Communication Scientifique Directe - HAL - CEA - Commissariat à l’énergie atomique, Nov 24, 2010

National audienceContexte, objectifs: La compréhension de la maladie à Chikungunya qui se caracté... more National audienceContexte, objectifs: La compréhension de la maladie à Chikungunya qui se caractérise par l'induction de douleur articulaire et musculaire chronique à long terme. Le laboratoire a développé un modèle d'infection expérimentale par le virus du Chikungunya chez le macaque cynomolgus afin d'explorer celle-ci à moyen et long terme. Résultats: Ce modèle reproduit lors de l'infection aigüe les signes cliniques et un profil d'évolution des paramètres virologiques et immunologiques proches de l'infection humaine. Nous avons identifié les sites de réplication virale et mis en évidence la persitance du virus dans les tissus ce qui permet pour la première fois de donner un début d'explication à la pathologie à long terme. Nous avons utilisé ce modèle pour évaluer une méthode prophylactique proposé lors de l'épidémie de la Réunion en 2006. Conclusion: Associé aux essais sur des modèles murins représentatifs de l'infection en phase aiguë, l'utilisation des primates non-humain est indispensable pour valider en préclinique des stratégies vaccinales ou prophylactiques s'appliquant à la période chronique de l'infection

Research paper thumbnail of Preclinical Evaluation of a Novel Epicutaneous Vaccine against Respiratory Syncytial Virus

International audienceIn order to be able to put an RSV vaccine onto the market, new vaccination ... more International audienceIn order to be able to put an RSV vaccine onto the market, new vaccination strategies combining scientific and technical innovation need to be explored. In the present project, we describe the development and the non-clinical evaluation of an original epicutaneous RSV vaccine that combines two patented technologies: Viaskin® epicutaneous patches developed by DBV Technologies as a delivery platform, and RSV N-nanorings fused to the F epitope targeted by palivizumab (N-FsII) developed by the French National Institute for Agronomical Research (INRA) as a subunit antigen. We have demonstrated that Viaskin® loaded with a formulation containing N-FsII antigen (Viaskin®- N-FsII) is highly immunogenic in mice and promote a Th1/Th17 oriented immune response. More importantly, Viaskin®-N-FsII epicutaneous vaccine confers a high level of protection against viral replication upon RSV challenge in mice, without exacerbating clinical symptoms. In swine, which provides the be...

Research paper thumbnail of La longueur de la tige de la neuraminidase d'un virus influenza aviaire H7N1 produit des effets opposés chez le poulet et le canard

National audienceOne of the host-range determinants that favor the multiplication of influenza vi... more National audienceOne of the host-range determinants that favor the multiplication of influenza viruses in domestic poultry is the length of the neuraminidase (NA) stalk: a deletion of about 20 amino acids in the NA-stalk is frequently detected upon transmission of influenza A viruses from waterfowl to domestic poultry and was recently associated with increased virulence in chicken. Whether this modification has any effect in ducks is currently unknown. Using reverse genetics, a recombinant virus derived from a turkey H7N1 influenza virus isolate with a short-stalk neuraminidase, A/turkey/Italy/977/1999, and an NA stalk insertion variant (insNA) were produced. Four-week-old chickens that were inoculated via the intratracheal and oral routes with the insNA virus showed a better survival and a lower oro-pharyngeal excretion than those inoculated with the wt-virus. The two viruses did not differ as regards viral loads in the lungs, kidneys and caeca, but the short-stalk NA virus induced...

Research paper thumbnail of Dystrophin expression after locoregional injection of rAAV8-U7SnRNA vectors in the forelimb of GRMD dogs

Research paper thumbnail of Mode of Delivery and Cell Tropism Versus Immunotoxicity of Recombinant AAV in Nonhuman Primate

Abstracts 8th Annual Meeting French Society of Cell and Gene Therapy, 21–23 June 2009, Faculté de... more Abstracts 8th Annual Meeting French Society of Cell and Gene Therapy, 21–23 June 2009, Faculté de Médecine de la Pitié-Salpêtrière Paris, France SFTCG 2009 Invited PresentationsInternational audienc

Research paper thumbnail of Assessment of TRPC1 and TRPC3 as Potential Therapeutic Targets for DMD Treatment in Complement to rAAV-microDystrophin Gene Therapy

Le Centre pour la Communication Scientifique Directe - HAL - memSIC, Apr 9, 2021

International audienc

Research paper thumbnail of Exploration of muscle from GRMD dogs transplanted with MuStem cells using "omics" approaches

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Oct 14, 2013

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Research paper thumbnail of Temperature variations during incubation and postnatal period affect performance, metabolism, health and gene expression in the blood of fast-growing chickens

Le Centre pour la Communication Scientifique Directe - HAL - Diderot, Sep 17, 2018

Research paper thumbnail of An aberrant age of liver DNA methylation is associated with cloning-induced pathologies

Le Centre pour la Communication Scientifique Directe - HAL - Université de Nantes, Nov 16, 2015

National audienceIt is postulated that the developmental defects frequently observed in somalie c... more National audienceIt is postulated that the developmental defects frequently observed in somalie clones arise from inappropriate reprogramming of the donor epigenome by the oocyte. We used cattle clones as a model to investigate the long­ lerm effects of nuclear reprogramming on both DNA methylation and the phenotype of a differentiated organ, the liver. Pathological perinatal clones and apparently normal adult clones, both produced within one decade, were studied, together with age-matched controls. We identified differentially methylated regions (DMRs) in gene promoters displaying variations according to age and to the clone status of the animals. Strikingly, whereas adult clones did not differ significantly from adult controls, perinatal clones showed a demethylation at DMRs inconsistent with their chronological age. Pathological features were found in the liver of perinatal clones only, with histological lesions and modifications to both histomorphometrical and metabolic parameters. The integration of DMRs with phenotypic datasets led to the identification of epigenetic alterations correlated to phenotypic abnormalities in perinatal clones. Genes important to the antioxidant response and energy metabolism were targeted by these alterations. For at !east one DMR, the aberrant methylation profile in perinatal clones was associated with altered gene expression. The liver defects encountered in pathological perinatal clones could be associated to the aberrant age of DNA methylation, at genes indicating potential deficits in oxidative metabolism. We propose that epigenetic ageing is an adaptation to the excessive oxidative stress induced by reprogramming that the pathological clones were not able to counteract during subsequent developmental stages

Research paper thumbnail of Effects of post-hatch fast of chick on digestive tract development and growth performance according to diet and rearing environmental conditions

In commercial conditions, chicks underwent a post-hatch fast (PHF) between 24 and 72h, and about ... more In commercial conditions, chicks underwent a post-hatch fast (PHF) between 24 and 72h, and about 24h when hatchery and farm are in the same region. Effects on digestive tract development (DTD) and animal growth are controversial due to several factors such as definition of bird age (from hatching in most studies, or from farm arrival), animal genetics, or dietary and environmental conditions (DEC). Here, the effect of PHF was studied on body weight (BW) and DTD of Ross PM3, during a first experiment (48h fast), with age of birds determined as the age at farm arrival with access to feed and water. To study the effect of DEC, birds were reared either in optimal DEC, or damaged DEC (low quality diet and/or low quality rearing environment) in a 2x2x2 factorial design (6 pens/treatment ; 54 birds/pen of 2.3 m2 of useful area). In a second experiment, the effect of a shorter PHF (24h) was studied on chick BW and DTD. In the first study, PHF showed effects on DTD, BW and animal health, dif...