References of "Defaweux, Valérie"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 57 (17 ULg)
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 ▲]

Detailed reference viewed: 33 (6 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 33 (11 ULg)
Peer Reviewed
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)
Peer Reviewed
See detailLa tremblante du mouton influence-t-elle le système immunitaire lors d’une réponse vis-à-vis d’un antigène
Defaweux, Valérie ULg; Dorban, G.; Demonceau, C. et al

Conference (2005, November)

Detailed reference viewed: 26 (15 ULg)
See detailL'infection par les prions pathogènes modifie l'expression menbranaire de la PrPc par les cellules dendritiques
Dorban, G; Demonceau,C; Levavasseur, E et al

Poster (2005, October)

Detailed reference viewed: 21 (15 ULg)
Full Text
Peer Reviewed
See detailCharacterization of bovine and human cellular prion protein expressed in the central nervous system and in lymphoid organs.
Defaweux, Valérie ULg; Stramiello, Sara; Capellari, Sabina et al

Poster (2005, 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 associate with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas, it is largely confined to the nervous system in 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. Given that the normal cellular prion protein (PrPC), is sine qua non for PrP-res formation and the development of TSE, it appears reasonable to hypothesize that tissue-specific PrPC properties may represent one of the host factors influencing the cell tropism of the infectious agent in human or bovine. We applied a western blot analyses to compare the relative percentage of the di-, mono- and unglycosylated PrPC (the so called glycoform ratio) as well as the expression of truncated PrPC forms in tissues from the central nervous system and lymphoid structures (lymphoid follicles, lymphocytes and follicular dendritic cells) of both bovine and human. We found that PrPC glycoform ratio is significantly different between cerebellum and medulla in both bovine and human. Moreover, the expression of truncated forms of PrPC (i.e. 21 and 18 kDa PrPC) was also significantly heterogenous according to the brain region investigated. PrPC was highly glycosylated in spleen and lymphoid follicles isolated from bovine tonsils, mesenteric lymph nodes, ileal and jejunal Peyer’s patches. After deglycosylation, a novel PrPC truncated form with a relative molecular mass of about 25 kDa was detected in bovine lymphoid organs beside the typical 18 and 21 kDa forms. No difference in WB PrPC profile was seen in human lymphocytes extracted either from spleen or tonsil. Our results highlight variation in the profile expression of PrPC in peripheral and central tissues of bovine and human. Such differences may have an implication for PrPC function or may represent critical factors influencing the accumulation of the infectious agent in these areas. Supported by the EU contract QLG3-CT-2002-81030. [less ▲]

Detailed reference viewed: 25 (3 ULg)
Peer Reviewed
See detailImplication of Peyer’s patches dendritic cells in prion diseases.
Dorban, G.; Defaweux, Valérie ULg; Demonceau, C. et al

Poster (2005, June)

Detailed reference viewed: 8 (1 ULg)
Peer Reviewed
See detailInvestigation of germinal centres in vivo and in vitro in the context of prion disease
Demonceau, C.; Defaweux, Valérie ULg; Flandroy, S. et al

Poster (2005, April)

Detailed reference viewed: 8 (2 ULg)
Peer Reviewed
See detailCellular and nervous environment of mouse mesenteric lymph node germinal centres
Wenders, Frédéric ULg; Dorban, G.; Piret, Joëlle ULg et al

Conference (2005, April)

Detailed reference viewed: 17 (0 ULg)
Peer Reviewed
See detailFollicular dendritic cells innervation within spleen of five mouse strains with different incubation periods after intraperitoneal BSE inoculation.
Demonceau, C.; Marshall, A.; Sales, J. et al

Poster (2005, February)

Detailed reference viewed: 13 (1 ULg)
Full Text
Peer Reviewed
See detailFollicular dendritic cells related to nerve fibres and cellular prion protein expression in ileal and jejunal Peyer’s patches of cows and calves
Defaweux, Valérie ULg; Antoine, Nadine ULg; Dorban, G. et al

Poster (2005, February)

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). Before neuroinvasion, early accumulation of infectious prion protein ... [more ▼]

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). Before neuroinvasion, early accumulation of infectious prion protein (PrPsc) takes place on follicular dendritic cells (FDC) which are resident cells in germinal centres. The strain, the infection pathway and the lesions in the central nervous system are similar between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt Jakob diseases. But in BSE, the agent tropism differs from lymphoid organs. Only bovine ileal PP are infectious. In order to study the replication and the possible ways of neuroinvasion of PrPsc in bovine PP, we studies the expression of cellular prion protein (PrPc), necessary for PrPsc accumulation, and compared the innervation of germinal centres related to FDC on ileal and jejunal PP of cows and calves. We performed classical immunoperoxydase staining and double immunofluorescence staining analyzed with a confocal microscopy. Differences in the innervation of germinal centres and expression of PrPc were evident. More contacts between FDC and nerve fibres are observed in calves PP. PrPc expression, carried out with different anti-PrPc antibodies, highlighted a heterogeneous labelling between calves and cows PP. Such results permit us to show that the innervation of PP is a dynamic process which could influence the first way of neuroinvasion in prion diseases. Moreover differences in the affinity of some antibody for PrPc allow us to postulate that PrPc glycoforms differ with age of bovines and thus could interfere with PrPsc tropism. [less ▲]

Detailed reference viewed: 13 (6 ULg)
Full Text
Peer Reviewed
See detailInterfaces between dendritic cells, other immune cells, and nerve fibres in mouse Peyer's patches: Potential sites for neuroinvasion in prion diseases
Defaweux, Valérie ULg; Dorban, Gauthier ULg; Demonceau, Christine ULg et al

in Microscopy Research and Technique (2005), 66(1), 1-9

In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to ... [more ▼]

In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to dendritic cells, viewed as candidate transporters of infectious prion. Double immunofluorescence labellings with anti-CD11c antibody and marker for other immune cells (B cells, T cells, follicular dendritic cells) were carried out and analysed by confocal microscopy on Peyer's patch cryosections. To reveal the extensive ganglionated networks of the myenteric and submucosal plexi and the sparse meshworks of nerve strands, we used antibodies directed against different neurofilament subunits or against glial fibrillary acidic protein. In the suprafollicular dome, dendritic cells connect, via their cytoplasmic extensions, enterocytes with M cells of the follicle-associated epithelium. They are also close to B and T cells. Nerve fibres are detected in the suprafollicular dome, notably in contact with dendritic cells. Similar connections between dendritic cells, T cells, and nerve fibres are seen in the interfollicular region. Germinal centres are not innervated; inside them dendritic cells establish contacts with follicular dendritic cells and with B cells. After immunolabelling of normal prion protein, dendritic cells of the suprafollicular dome are intensely positive labelled. (c) 2005 Wiley-Liss, Inc. [less ▲]

Detailed reference viewed: 48 (17 ULg)
See detailDistribution of nerve fibers and prion protein expression in mouse Peyer's patches
Defaweux, Valérie ULg; Dorban, G; Demonceau, C et al

Poster (2004, July)

Detailed reference viewed: 7 (3 ULg)
Full Text
Peer Reviewed
See detailFDC-B1: a new monoclonal antibody directed against bovine follicular dendritic cells
Defaweux, Valérie ULg; Mélot, France ULg; Jolois, Olivier ULg et al

in Veterinary Immunology and Immunopathology (2004), 97(1-2), 1-9

Follicular dendritic cells (FDCs) are a unique population of accessory cells located in the light zone of the germinal centres of lymphoid follicles. Their involvement in the generation of Immoral immune ... [more ▼]

Follicular dendritic cells (FDCs) are a unique population of accessory cells located in the light zone of the germinal centres of lymphoid follicles. Their involvement in the generation of Immoral immune responses implies a potential role for these cells in many disorders. Indeed, in prion diseases, FDCs seem to be the major sites of extraneuronal cellular prion protein expression and the principal sites of the infectious agent accumulation in lymphoid organs. The identification of FDC is useful for the analysis of their distribution in reactive lymphoid tissue as well as in pathological conditions. The production and characterisation of a new mouse monoclonal antibody directed against bovine follicular dendritic cells (FDC-B1) is reported. The antigen detected by FDC-B1 is expressed exclusively on the surface of FDCs in ruminant lymphoid organs. The antigen has an approximate molecular weight of 28 kDa. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

Detailed reference viewed: 55 (20 ULg)
Peer Reviewed
See detailDistribution of nerve fibres and prion protein expression in mice Peyer’s patches
Defaweux, Valérie ULg; Dorban, G.; Demonceau, C. et al

Poster (2003, October)

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). The antigens enter into the underlying lymphoid tissue organized in PP ... [more ▼]

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). The antigens enter into the underlying lymphoid tissue organized in PP through the medium of M cells. Infectious prion protein (PrPres) would probably take the same way of entry and like this initiate the first stage of lympho-invasion. Theoretically, intestinal lymphoid cells can come in contact with ingested PrPres and with nerve endings of the intramural system. The distribution pattern of the nerve fibres and lymphoid cells in PP and possible contact between these two elements implicated in neuroinvasion are not yet fully elucidated. In our study, classical immunoperoxydase staining and double immunofluorescence staining analysed with a confocal microscope has been carried out on C56Bl/6 mice PP. Immunoperoxidase and immunofluorescent CD11c stainings show numerous dendritic cells (DC) in the suprafollicular dome, close to the epithelium made of enterocytes and M-cells. Confocal studies show the presence of DC in the T cell zones of Peyer's patches, and also close to B cells in the follicule and to follicular dendritic cells (FDC) in the germinal centres. The PrPc expression, fundamental in the pathogenesis of prion diseases, is notably localized in germinal centres, co-localized with the FDC network and on cellular structures close to the epithelium, co-localized with DC. Nerve fibres have been immunostained in fluorescence using antibodies raised against neurofilaments High, Medium and Low and against glial fibrillary acidic protein (GFAP). Only GFAP staining revealed the presence of some nerve fibres in the suprafollicular dome, coursing the mucosal epithelium and also at the periphery of germinal centres in close connection with numerous dendritic cells. Such results permit us to postulate that these nerve fibres and PrPc positive dendritic cells, strategically positioned under the intestinal epithelium as well as in the germinal centres close to FDC network, highly expressing PrPc and thought to replicate PrPres, may be involved in the peripheral transport of the infectious prion protein. [less ▲]

Detailed reference viewed: 18 (5 ULg)