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Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion

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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.

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Acknowledgements

We acknowledge the technical assistance of Dr. P. Hubert. We thank Professor E. Heinen from the Human Histology Unit of The Faculty of Medicine of the University of Liege who kindly provided the FDC-B1 monoclonal antibody.

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  1. Vinciane Toppets

    Present address: Department of Morphology and Pathology, Laboratory of Animal Histology and Embryology, Faculty of Veterinary Medicine, University of Liege, Boulevard de Colonster, 20 Bat. B43a, 4000, Liege, Belgium

Authors and Affiliations

  1. Department of Morphology and Pathology, Laboratory of Animal Histology and Embryology, Faculty of Veterinary Medicine, University of Liege, Boulevard de Colonster, 20 Bat. B43a, 4000, Liege, Belgium

    Joelle Piret, Luc Grobet & Nadine Antoine

  2. Animal Physiology, Veterinary Department, Faculty of Sciences, University of Namur FUNDP, Namur, Belgium

    Nathalie Kirschvink

  3. Laboratory of Infectious Pathology and Immunology, INRA, Nouzilly, France

    Frederic Lantier, Isabelle Lantier & Patricia Berthon

  4. DNA-Vision Agrifood, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium

    Georges Daube

  5. Department of Animal productions, Biostatistic and Bioinformatic Applied to Veterinary Sciences Unit, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium

    Laurent Massart

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  1. Vinciane Toppets
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Correspondence to Vinciane Toppets.

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Toppets, V., Piret, J., Kirschvink, N. et al. Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion. Cell Tissue Res 348, 167–176 (2012). https://doi.org/10.1007/s00441-012-1376-x

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