Neuroimmune connections in jejunal and ileal Peyer's patches at various bovine ages: potential sites for prion neuroinvasion

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 ▲]

Ultrasonography and histology of equine menisci; a comparative study of the medial

Poster (2007, January)

Comparative ultrasonographic and morphologic appearance of femorotibial menisci in horses: a preliminary study

in Canifelis Hippos Proceedings (2007)

Distribution of nerve fibres in bovine and human mucosal associated lymphoid tissues

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 ▲]

Morphological alterations in oxidative muscles associated with equine atypical myopathy

Poster (2006, August)

Biological characterization of bovine herpesvirus 1 recombinants possessing the vaccine glycoprotein E negative phenotype

in Veterinary Microbiology (2006), 113(3-4), 283-291

Intramolecular recombination is a frequent event during the replication cycle of bovine herpesvirus 1 (BoHV-1). Recombinant viruses frequently arise and survive in cattle after concomitant nasal ... [more ▼]

Intramolecular recombination is a frequent event during the replication cycle of bovine herpesvirus 1 (BoHV-1). Recombinant viruses frequently arise and survive in cattle after concomitant nasal infections with two BoHV-1 mutants. The consequences of this process, related to herpesvirus evolution, have to be assessed in the context of large use of live marker vaccines based on glycoprotein E (gE) gene deletion. In natural conditions, double nasal infections by vaccine and wild-type strains are likely to occur. This situation might generate virulent recombinant viruses inducing a serological response indistinguishable from the vaccine one. This question was addressed by generating in vitro BoHV-1 recombinants deleted in the gE gene from seven wild-type BoHV-1 strains and one mutant strain deleted in the genes encoding gC and gE. In vitro growth properties were assessed by virus production, one step growth kinetics and plaque size assay. Heterogeneity in the biological properties was shown among the investigated recombinant viruses. The results demonstrated that some recombinants. in spite of their gE minus phenotype, have biological characteristics close to wild-type BoHV-1. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

Histological study of the horse stifle menisci in relation with ultrasonographic aspect: preliminary study

in Italian Journal of Anatomy and Embryology (2006), 111

Characterization of bovine and human cellular prion protein expressed in the central nervous system and in lymphoid organs.

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 ▲]

Implication of Peyer’s patches dendritic cells in prion diseases.

Poster (2005, June)

Cellular and nervous environment of mouse mesenteric lymph node germinal centres

Conference (2005, April)