title: Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion.
abstract: Recent studies have established the involvement of nasal-associated lymphoid tissues, mainly the pharyngeal tonsil, in prion pathogenesis. However, the mechanisms of the associated neuroinvasion are still debated. To determine potential sites for prion neuroinvasion inside the ovine pharyngeal tonsil, the topography of heavy (200 kDa) and light (70 kDa) neurofilaments and of glial fibrillar acidic protein has been semi-quantitatively analysed inside the various compartments of the tonsil. The results show that the most innervated areas are the interfollicular area and the connective tissue located beneath the respiratory epithelium. The existence of rare synapses between follicular dendritic cells and nerve fibres inside the germinal centre indicates that this mechanism of neuroinvasion is possible but, since germinal centres of lymphoid follicles are poorly innervated, other routes of neuroinvasion are likely. The host PRNP genotype does not influence the pattern of innervation in these various tonsil compartments, unlike ageing during which an increase of nerve endings occurs in a zone of high trafficking cells beneath the respiratory epithelium. A minimal age-related increase of innervation inside the lymphoid follicles has also been observed. An increase in nerve fibre density around the lymphoid follicles, in an area rich in mobile cells such as macrophages and dendritic cells capable of capturing and conveying pathogen prion protein (PrPd), might ensure more efficient infectivity, not in the early phase but in the advanced phase of lymphoinvasion after the amplification of PrPd; alternatively, this area might even act as a direct site of entry during neuroinvasion.
authors.affiliation: Department of Morphology and Pathology, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. vtoppets@ulg.ac.be
authors.forename: Vinciane
authors.initials: V
authors.lastname: Toppets
authors.forename: Joelle
authors.initials: J
authors.lastname: Piret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kirschvink
authors.forename: Frederic
authors.initials: F
authors.lastname: Lantier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lantier
authors.forename: Patricia
authors.initials: P
authors.lastname: Berthon
authors.forename: Georges
authors.initials: G
authors.lastname: Daube
authors.forename: Laurent
authors.initials: L
authors.lastname: Massart
authors.forename: Luc
authors.initials: L
authors.lastname: Grobet
authors.forename: Nadine
authors.initials: N
authors.lastname: Antoine
mesh_terms: D000234:Adenoids / Q000276:immunology* / Q000294:innervation*; D000375:Aging / Q000473:pathology; D000818:Animals; D016616:Cryoultramicrotomy; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000473:pathology; D005838:Genotype; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009420:Nervous System / Q000276:immunology* / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000276:immunology / Q000473:pathology; D034561:Sheep, Domestic / Q000276:immunology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D011328:Prions; C044882:neurofilament protein L; C051774:neurofilament protein H