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.

A ganglion cell cluster along the glossopharyngeal nerve near the human palatine tonsil

“…However, a ganglion cell would be likely to carry multiple peripheral axons towards the tonsil. Neuroimmune connections can occur in the palatine tonsil [13,14], and the ganglion cells may become an initial site of prion infection [15]. Therefore, the clinical relevance of the presence of a ganglion seems to be greater than the well-known gustatory sensory fibers of the nerve.…”

Transmission Properties of Pathogenic Protein Agents in Human Prion Disease and Neurodegenerative Diseases

“…Other than the GI tract, alternative entry pathways of prions have also been identified, such as transports via skeletal muscle cells and papillae in the tongue [88,89], and via the olfactory nerve to the olfactory bulb through oral and nasal mucosa [90][91][92][93][94][95] as lesions of the olfactory epithelium accelerated prion neuroinvasion and disease onset [96]. In addition to food, other infectious pathways, particularly in non-human animals, include mites [97], fly larvae and pupae [98], saliva (via the oral route) and blood (via transfusion) [99], gingival scarification [100], pharyngeal tonsil [101,102], and skin scarification of skin or gums [103]. In human CJD patients, prion protein was detected in nasal brushings with very high sensitivity and specificity [104], suggesting this venue may need to be addressed to prevent human CJD transmission.…”

Lymph Drainage from the Ovine Tonsils: An Anatomical Study of the Tonsillar Lymph Vessels

“…To aid the unravelling of the pathogenesis of transmissible spongiform encephalopathies (TSEs), morphological and immunological data on the five ovine tonsils, including the paired palatine tonsil [tonsilla (t.) palatina] located in the oropharynx, the paired paraepiglottic tonsil (t. paraepiglottica) in the laryngopharynx, and the tonsil of the soft palate (t. veli palatina), the pharyngeal tonsil (t. pharyngea) and the paired tubal tonsils (t. tubaria) in the nasopharynx (Casteleyn et al., , ; Breugelmans et al., ), were gathered. The exact anatomical localizations, histological characteristics, volumes and surface areas, distribution of lymphoid cell populations and innervation of the ovine tonsils have yet been described (Casteleyn et al., , , ; Russo et al., ; Breugelmans et al., ,b,c; Toppets et al., ).…”