Anatomical evidence for ileal Peyer’s patches innervation by enteric nervous system: a potential route for prion neuroinvasion?

Abstract

We have examined the innervation of the gut-associated lymphoid system of the sheep ileum, with a view to identifying potential sites for neuroinvasion by pathogens, such as prions (PrP(Sc)). Special attention has been paid to the follicles of Peyer's patches (PPs), which are major sites of PrP(Sc) accumulation during infection. Evidence exists that the enteric nervous system, together with the parasympathetic and sympathetic pathways projecting to the intestine, are important for PrP(Sc) entry into the central nervous system. Thus, PrP(Sc) might move from PPs to the neurons and nerve fibres that innervate them. We investigated, by immunohistochemistry and retrograde tracing (DiI) from the follicles, the distribution and phenotype of enteric neurons innervating the follicles. Antibodies against protein gene product 9.5, tyrosine hydroxylase, dopamine beta hydroxylase, choline acetyltransferase, calbindin (CALB), calcitonin gene-related peptide (CGRP), and nitric oxide synthase were used to characterise the neurons. Immunoreactivity for each of these was observed in fibres around and inside PP follicles. CGRP-immunoreactive fibres were mainly seen at the follicular dome. Retrograde tracing revealed submucosal neurons that contributed to the innervation of PPs, including Dogiel type II neurons and neurons immunoreactive for CALB and CGRP. The major source of the adrenergic fibres are the sympathetic ganglia. Our results thus suggest that enteric and sympathetic neurons are involved during the first stage of neuroinvasion, with neurons connecting to them acting as potential carriers of PrP(Sc) to the central nervous system.

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

“…Previously we have also demonstrated that CD11c-DCs established a lot of contacts with the nerve Wbers inside the mouse Peyer's patches in physiological conditions and following a scrapie challenge (Defaweux et al 2005;Dorban et al 2007a). Similar results have been obtained within sheep Peyer's patches (Marruchella et al 2007;Chiocchetti et al 2008). The molecular basis of these neuroimmune interfaces between DCs and PNS could implicate a ligand-receptor connection via the muscarinic acetylcholine M2 receptor (Ma et al 2007) or involve TNT (Gousset et al 2009).…”

Blockade of Nitric Oxide Synthesis Modulates Rat Immunoglobulin A

“…Our previous data have suggested possible involvement of NO in the acute effect of ethanol on rat intestinal IgA expression [29] . Recent studies demonstrating NOS-ir fibers within ileal Peyer's patches in sheep [30] as well as a regulatory role of iNOS in both T-cell-dependent and T-cell-independent IgA class switch recombination in mice [31] substantiate the immunomodulatory role of NO in the gastrointestinal tract.…”

Les prions exploitent les communications neuro-immunitaires

“…Contrairement à ce dernier, il réagit de façon asymptomatique à l'infection. Des résultats obtenus par diverses équipes ont montré que la présence de PrP Sc ne compromettait pas l'établissement d'interfaces neuro-immunes dans les organes lymphoïdes périphériques [29,30]. Ces résultats laissent supposer que, contrairement aux neurones centraux, les neurones périphériques semblent pouvoir être infectés sans être affectés dans leur fonctionnement par les prions.…”