References of "Defaweux, Valérie"
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See detailTravaux pratiques en Histologie Humaine, Quadrimestre 4, 5 et 6
Defaweux, Valérie ULg; Mélot, France ULg; Florquin, Sandra ULg et al

Learning material (2010)

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See detailImmunological discrimination between self and non self
Defaweux, Valérie ULg; Heinen, Ernst ULg

in Encyclopedia of Life Sciences (2010)

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See detailVaccination with class-I restricted PrP peptides induces cytotoxic CD8+ T cells and prolongs the clinical phase duration of murine scrapie
Bruley Rosset, Martine; Sacquin, Antoine; Defaweux, Valérie ULg et al

Poster (2009, October)

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See detailGerminal centre innervation of bovine and human tonsils related to prion diseases.
Defaweux, Valérie ULg; Dorban, Gauthier; Antoine, Nadine ULg et al

in Brain, Behavior & Immunity (2009), 23(1), 10

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See detailIntroduction à la Cytologie et à l'Histologie générale
Defaweux, Valérie ULg

Learning material (2009)

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See detailIn vitro modelisation of prions neuroinvasion mediated by dendritic cells
Dorban, G.; Defaweux, Valérie ULg; Heinen, Ernst ULg et al

Poster (2008, October)

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See detail. Do innervation of germinal centre and contacts between FDC and nerve fibers be keys to understand the susceptibility difference between bovines and humans to the BSE agent?
Defaweux, Valérie ULg; Dorban, G.; Antoine, Nadine ULg et al

Poster (2008, October)

Background: In regard to BSE and vCJD, the agent tropism for lymphoid tissues is completely different even if the infectious strain responsible and the way of inoculation are identical. During vCJD, the ... [more ▼]

Background: In regard to BSE and vCJD, the agent tropism for lymphoid tissues is completely different even if the infectious strain responsible and the way of inoculation are identical. During vCJD, the infectious agent crosses the digestive barrier and multiplies in lymphoid organs, before progressively reaching the brain. Indeed, in vCJD, it accumulates in the ileum, tonsils, spleen and appendix of infected individuals. In contrast, in cattle, the BSE agent has a low affinity for lymphoid tissues and mainly accumulates in the nervous system. During preclinical stages, infectivity, other than that in the peripheral nervous system or central nervous system, is confined in the distal ileum of orally infected cattle. So, it appears that, at least in the case of BSE and vCJD, host properties can influence the accumulation of the infectious agent in lymphoid organs. Objectives and methods: In this study, we analysed by confocale microscopy the mucosal innervation and the interface between nerve fibres and FDC in bovine and human tonsils using a panel of antibodies. Since differences in the innervation of lymphoid organs depending on species and on age have been reported, we analysed two categories of bovines (calves less than 12 months old and bovines older than 24 months) and two categories of humans (patients less than 5 years old and patients older than 25 years). Results: In both species, ways of innervation by-passing germinal centres could be postulated: nerve fibres are widely distributed in antigen/cell traffic area: the lamina propria, the interfollicular zone and the lymphoepithelial area. We pointed out that, only in tonsils of bovines older than 24 months, nerve fibres are observed to be in contact with FDC. In contrast, in human tonsils, no nerve fibres established contacts with FDC, whatever the age. Discussion: Innervation of germinal centres can be said to be an age-dependent dynamic process in bovines. The weak innervation of the secondary lymphoid organs could thus be a rate-limiting step to neuroinvasion in humans. This species difference could influence the way of neuroinvasion and thus, the susceptibility of bovines and humans to the BSE agent. [less ▲]

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See detailInteraction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure
Dorban, Gauthier ULg; Defaweux, Valérie ULg; Demonceau, Christine ULg et al

in Virchows Archiv (2007), 451(6), 1057-1065

In transmissible spongiform encephalopathies (TSEs), the infectious agent, called PrPsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting ... [more ▼]

In transmissible spongiform encephalopathies (TSEs), the infectious agent, called PrPsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting the nervous system. To clarify the cellular requirements for the neuro-invasion of the scrapie agent from the lymphoid organs to the central nervous system, we have studied, by confocal microscopy, the innervations within Peyer's patches, mesenteric lymph nodes and the spleen of mice in physiological conditions and after oral exposure to prion. Contacts between nerve fibres and PrPsc-associated cells, dendritic cells (DCs) and follicular dendritic cells (FDCs), were evaluated in preclinical prion-infected mice. Using a double immunolabelling strategy, we demonstrated the lack of innervation of PrPsc-accumulating cells (FDCs). Contacts between nerve fibers and PrPsc-propagating cells (DCs) were detected in T-cell zones and cell-trafficking areas. This supports, for the first time, the possible implication of dendritic cells in the prion neuroinvasion process. [less ▲]

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See detailDialogue between peripheral nervous system and immunity: a confocal exploration
Dorban, G.; Defaweux, Valérie ULg; Demonceau, C. et al

Poster (2007, November)

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See detailOral scrapie infection modifies the homeostasis of Peyer's patches' dendritic cells
Dorban, Gauthier ULg; Defaweux, Valérie ULg; Levavasseur, Etienne et al

in Histochemistry & Cell Biology (2007), 128(3), 243-251

In transmitted prion diseases the immune system supports the replication and the propagation of the pathogenic agent (PrPSc). DCs, which are mobile cells present in large numbers within lymph organs, are ... [more ▼]

In transmitted prion diseases the immune system supports the replication and the propagation of the pathogenic agent (PrPSc). DCs, which are mobile cells present in large numbers within lymph organs, are suspected to carry prions through the lymphoid system and to transfer them towards the peripheral nervous system. In this study, C57Bl/6 mice were orally inoculated with PrPSc (scrapie strain 139A) and sacrificed at the preclinical stages of the disease. Immunolabelled cryosections of Peyer's patches were analysed by confocal microscopy. Membrane prion protein expression was studied by flow cytometry. In Peyer's patches (PP), dissected at day one and day 105 after oral exposure to scrapie, we observed an increased population of DCs localised in the follicular-associated epithelium. On day 105, PrPSc was found in the follicles inside the PP of prion-infected mice. A subset of Peyer's patches DCs, which did not express cellular prion protein on their surface in non-infected mice conditions, was prion-positive in scrapie conditions. Within Peyer's patches oral scrapie exposure thus induced modifications of the homeostasis of DCs at the preclinical stages of the disease. These results give new arguments in favour of the implication of DCs in prion diseases. [less ▲]

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See detailNeuroimmune connections in jejunal and ileal Peyer's patches at various bovine ages: potential sites for prion neuroinvasion
Defaweux, Valérie ULg; Dorban, Gauthier ULg; Antoine, Nadine ULg et al

in Cell & Tissue Research (2007), 329(1), 35-44

During preclinical stages of cattle orally infected with bovine spongiform encephalopathy (BSE), the responsible agent is confined to ileal Peyer's patches (IPP), namely in nerve fibers and in lymph ... [more ▼]

During preclinical stages of cattle orally infected with bovine spongiform encephalopathy (BSE), the responsible agent is confined to ileal Peyer's patches (IPP), namely in nerve fibers and in lymph follicles, before reaching the peripheral and central nervous systems. No infectivity has been reported in other bovine lymphoid organs, including jejunal Peyer's patches (JPP). To determine the potential sites for prion neuroinvasion in IPP, we analyzed the mucosal innervation and the interface between nerve fibers and follicular dendritic cells (FDC), two dramatic influences on neuroinvasion. Bovine IPP were studied at three ages, viz., newborn calves, calves less than 12 months old, and bovines older than 24 months, and the parameters obtained were compared with those of JPP. No differences in innervation patterns between IPP and JPP were found. The major difference observed was that, in calves of less than 12 months, IPP were the major mucosal-associated lymphoid organ that possessed a large number of follicles with extended FDC networks. Using a panel of antibodies, we showed that PP in 24-month-old bovines were highly innervated at various strategic sites assumed to be involved in the invasion and replication of the BSE pathogen: the suprafollicular dome, T cell area, and germinal centers. In PP in calves of less than 12 months old, no nerve fibers positive for the neurofilament markers NF-L (70 kDa) and NF-H (200 kDa) were observed in contact with FDC. Thus, in view of the proportion of these protein subunits present in neurofilaments, the innervation of the germinal centers can be said to be an age-dependent dynamic process. This variation in innervation might influence the path of neuroinvasion and, thus, the susceptibility of bovines to the BSE agent. [less ▲]

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See detailL’interface neuro-immune et l’expression de la protéine prion cellulaire dans le cadre des maldies à prions. Une étude comparative des espèces bovine et humaine.
Defaweux, Valérie ULg

Doctoral thesis (2007)

Le tropisme cellulaire des prions infectieux diffère selon l’espèce animale, celui-ci est corrélé à la souche infectieuse et à des facteurs spécifiques de l’hôte. Par exemple, certains prions infectieux ... [more ▼]

Le tropisme cellulaire des prions infectieux diffère selon l’espèce animale, celui-ci est corrélé à la souche infectieuse et à des facteurs spécifiques de l’hôte. Par exemple, certains prions infectieux sont lymphotropiques, notamment en cas de scrapie chez les moutons et de variant de la maladie de Creutzfeldt-Jakob (vMCJ) chez l’homme. Par opposition, certains prions se caractérisent par un neurotropisme comme observé chez des patients Creutzfeldt-Jakob atteints de la forme sporadique ou chez des bovins atteints d’encéphalopathies spongiformes bovines (ESB). L’hypothèse de notre travail repose sur les observations suivantes : dans le cas du variant de la maladie de Creutzfeldt-Jakob et des encéphalopathies spongiformes bovines, l’agent responsable est identique, la voie d’inoculation et les lésions neurologiques le sont également, seul le tropisme de cette souche pour les organes lymphoïdes diffère. En effet, les amygdales, la rate et l’appendice sont infectieux chez l’homme. Par contre, l’infectiosité est surtout confinée au niveau du système nerveux chez le bovin. Lors d’une inoculation expérimentale par voie orale de l’agent responsable de l’ESB chez les bovins, les plaques de Peyer iléales sont les seuls tissus lymphoïdes infectieux. Notre hypothèse de travail est que des propriétés de l’hôte interviennent dans le tropisme de l’agent infectieux. Deux axes de recherche ont été envisagés afin de vérifier cette hypothèse :  L’analyse de la distribution des fibres nerveuses au sein des tissus lymphoïdes associés aux muqueuses (MALT) des espèces bovine et humaine  L’étude de l’expression de PrPc et de ses isoformes au sein des tissus lymphoïdes et nerveux des espèces bovine et humaine. Pour atteindre au mieux nos objectifs, il nous manquait un outil essentiel permettant la caractérisation spécifique des FDC bovines. En effet, aucun marqueur spécifique de ces cellules n’était commercialisé. Nous avons donc produit, en collaboration avec le Centre d’Economie Rural de Marloie, un anticorps monoclonal spécifiquement dirigé contre les cellules folliculaires dendritiques (FDC) bovines. Cet anticorps nous a permis d’étudier la distribution des FDC au sein des organes lymphoïdes bovins. Une attention particulière a été portée aux FDC isolées à partir des plaques de Peyer jéjunales (PPJ) et iléales (PPI). L’apparente différence d’infectivité de ces tissus lymphoïdes chez des bovins atteints expérimentalement d’ESB nous a conduit à comparer les capacités fonctionnelles des FDC isolées à partir de PPJ et de PPI. Ces observations sont décrites et discutées dans le chapitre 1. Dans le chapitre 2, nous avons établi une cartographie des fibres nerveuses au sein des amygdales, des plaques de Peyer iléales et jéjunales bovines de plusieurs catégories d’âge et ensuite comparé ce pattern d’innervation à celui des amygdales humaines; ceci permettra de pister les voies potentielles de neuro-invasion. Une attention particulière a été portée à l’interface cellules folliculaires dendritiques – fibres nerveuses. En effet, les FDC matures jouent un rôle prépondérant dans la pathogenèse des maladies à prion puisqu’en leur absence, une infection périphérique n’a pas lieu. De plus, la proximité entre fibres nerveuses et FDC est un paramètre intervenant dans la neuro-invasion; nous avons dès lors aussi analysé les contacts entre les FDC et les éléments nerveux. L’expression de la PrPc est une condition sine qua non pour la formation de PrPres. Cette protéine cellulaire sert probablement de récepteur pour son homologue infectieux mais sert surtout de substrat pour l’amplification de PrPres ; toute modification au niveau de sa synthèse pourrait entraîner un changement de la cinétique d’infection et pourrait expliquer l’apparente absence d’infectivité constatée au niveau du système immunitaire chez les bovins. L’expression tissulaire et cellulaire spécifique d’isoformes de la PrPc représente un facteur de l’hôte potentiellement capable d’influencer le tropisme cellulaire de l’agent infectieux chez l’humain et le bovin. Cette expression a été étudiée dans les systèmes MALT bovins et humains. Pour affiner notre étude, nous avons analysé, par des techniques de western-blotting, le glycopattern de la PrPc ainsi que l’expression de ses formes tronquées dans les tissus lymphoïdes humains et bovins mais également dans des populations cellulaires spécifiques, les lymphocytes et les FDC. Afin de vérifier si les isoformes de PrPc sont spécifiques aux tissus lymphoïdes, nous avons effectué une étude comparative du pattern de glycosylation et du ratio des formes clivées de PrPc, exprimés au sein de différentes régions du système nerveux central bovin et humain. Les résultats de ces travaux sont repris dans le chapitre 3. [less ▲]

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See detailDistribution of nerve fibres in bovine and human mucosal associated lymphoid tissues
Defaweux, Valérie ULg; Dorban, G.; Antoine, Nadine ULg et al

Poster (2006, October)

Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD ... [more ▼]

Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD, but little, if any, in sCJD or BSE. In particular, the BSE strain is associated with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas it is largely confined to the nervous system in infected cattle. Therefore, at least in the case of BSE and vCJD, it appears that host properties can influence the accumulation of the infectious agent in lymphoid organs. Mature FDC play an important role in prion pathogenesis, since neuroinvasion following peripheral challenge is significantly impaired in their absence. The proximity between these FDC and sympathetic nerve endings is known to affect the speed of prion neuroinvasion. In this study, we analysed the mucosal innervation and the interface between nerve fibres and FDC in bovine and human tonsils and in ileal and jejunal bovine Peyer’s patches using a panel of antibodies observed by confocal microscopy. Since differences in the innervation of lymphoid organs depending on age have been reported, we analysed three categories of bovine ages (new born calves, calves less than 12 months old and bovines older than 24 months) and two categories of human ages (patients less than 5 years old and patients older than 25 years). In both species, hypothetical ways of innervation by-passing germinal centre could be postulated: nerve fibres are widely distributed in antigens/cells traffic area (the lamina propria, the interfollicular zone, the suprafollicular dome in Peyer’s patches and the lymphoepithelial area in tonsils). We pointed out that, only in ileal and jejunal Peyer’s patches and in tonsils of bovines older than 24 months, nerve fibres are observed to be in contact with FDC. In contrast, in human tonsils, no nerve fibres established contact with FDC, whatever the age. Thus, innervation of germinal centres can be said to be an age-dependent dynamic process in bovines and a weak innervation of the secondary lymphoid organs could thus be a rate-limiting step to neuroinvasion in humans. This variation could influence the way of neuroinvasion and thus, the differences of susceptibility of bovines and humans to the BSE agent. [less ▲]

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See detailDendritic cells: potential actors in prion neuroinvasion.
Dorban, G.; Lallemand, C.; Defaweux, Valérie ULg et al

Poster (2006, September)

Detailed reference viewed: 11 (7 ULg)