Cell and Tissue Research

, Volume 332, Issue 2, pp 185–194 | Cite as

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

  • Roberto ChiocchettiEmail author
  • Gemma Mazzuoli
  • Valeria Albanese
  • Maurizio Mazzoni
  • Paolo Clavenzani
  • Giovanna Lalatta-Costerbosa
  • Maria L. Lucchi
  • Giovanni Di Guardo
  • Giuseppe Marruchella
  • John B. Furness
Regular Article


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 (PrPSc). Special attention has been paid to the follicles of Peyer’s patches (PPs), which are major sites of PrPSc accumulation during infection. Evidence exists that the enteric nervous system, together with the parasympathetic and sympathetic pathways projecting to the intestine, are important for PrPSc entry into the central nervous system. Thus, PrPSc 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 β 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 PrPSc to the central nervous system.


Intestinal immune system Enteric nervous system Peyer’s patches DiI Prion diseases Sheep 



The careful technical assistance of Caterina Mongardi-Fantaguzzi is gratefully acknowledged.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Roberto Chiocchetti
    • 1
    Email author
  • Gemma Mazzuoli
    • 1
  • Valeria Albanese
    • 2
    • 3
  • Maurizio Mazzoni
    • 1
  • Paolo Clavenzani
    • 1
  • Giovanna Lalatta-Costerbosa
    • 1
  • Maria L. Lucchi
    • 1
  • Giovanni Di Guardo
    • 2
  • Giuseppe Marruchella
    • 2
  • John B. Furness
    • 3
  1. 1.Department of Veterinary Morphophysiology and Animal ProductionsUniversity of BolognaBolognaItaly
  2. 2.Department of Comparative Biomedical SciencesUniversity of TeramoTeramoItaly
  3. 3.Department of Anatomy and Cell BiologyUniversity of MelbourneParkvilleAustralia

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