1887

Abstract

Disease-associated prion protein (PrP) in the enteric nervous system (ENS) of 20- to 24-month-old Suffolk sheep in the late subclinical and early clinical phase of scrapie was studied. Sites in the alimentary tract extending from the forestomachs and abomasum to the colon from scrapie-affected sheep (PrP) and scrapie-resistant sheep (PrP and PrP) were examined. PrP was found only in scrapie-affected sheep and was most prominent in the ENS when abundant deposits of PrP were also present in adjacent lymphoid nodules. Immunolabelling with the nerve fibre markers PgP 9.5 and neuron-specific enolase and the satellite cell marker glial fibrillary acidic protein revealed the extensive ganglionated networks of the myenteric and submucosal plexi. Fewer nerve fibres were present in the lamina propria, T-cell dominated interfollicular areas and dome regions of Peyer's patches. A substantial network of nerve fibres was detected in many lymphoid nodules of both the scrapie-affected and scrapie-resistant sheep. Nerve fibres were also detected within the capsule of lymphoid nodules. Electron microscopy revealed the presence of nerves in the lymphoid nodules, showing a close association with follicular dendritic cells, lymphocytes and tingible body macrophages. In demonstrating that lymphoid nodules in the Peyer's patches of scrapie-affected sheep possess a substantial network of nerve fibres, the present study shows that nodules provide close contact between nerve fibres and cell populations known to contain abundant PrP, including follicular dendritic cells and tingible body macrophages, and that gut-associated lymphoid nodules in sheep may represent an important site for neuroinvasion.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.18874-0
2003-05-01
2019-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/5/vir841327.html?itemId=/content/journal/jgv/10.1099/vir.0.18874-0&mimeType=html&fmt=ahah

References

  1. Andréoletti, O., Berthon, P., Marc, D., Sarradin, P., Grosclaude, J., van Keulen, L., Schelcher, F., Elsen, J.-M. & Lantier, F. ( 2000; ). Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81, 3115–3126.
    [Google Scholar]
  2. Baldauf, E., Beekes, M. & Diringer, H. ( 1997; ). Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord. J Gen Virol 78, 1187–1197.
    [Google Scholar]
  3. Balemba, O. B., Mbassa, G. K., Semuguruka, W. D., Assey, R. J., Kahwa, C. K. B., Hay-Schmidt, A. & Dantzer, V. ( 1999; ). The topography, architecture and structure of the enteric nervous system in the jejunum and ileum of cattle. J Anat 195, 1–9.[CrossRef]
    [Google Scholar]
  4. Beekes, M. & McBride, P. A. ( 2000; ). Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett 278, 181–184.[CrossRef]
    [Google Scholar]
  5. Beekes, M., Baldauf, E. & Diringer, H. ( 1996; ). Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. J Gen Virol 77, 1925–1934.[CrossRef]
    [Google Scholar]
  6. Beekes, M., McBride, P. A. & Baldauf, E. ( 1998; ). Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79, 601–607.
    [Google Scholar]
  7. Begara-McGorum, I., Clark, A. M., Martin, S. & Jeffrey, M. ( 2000; ). Prevalence of vacuolar lesions consistent with scrapie in the brains of healthy cull sheep of the Shetland Islands. Vet Rec 147, 439–441.[CrossRef]
    [Google Scholar]
  8. Bencsik, A., Lezmi, S. & Baron, T. ( 2001a; ). Autonomous nervous system innervation of lymphoid territories in spleen: a possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie. J Neurovirol 7, 447–453.[CrossRef]
    [Google Scholar]
  9. Bencsik, A., Lezmi, S., Hunsmann, G. & Baron, T. ( 2001b; ). Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. Dev Immunol 8, 235–241.[CrossRef]
    [Google Scholar]
  10. Brown, K. L., Stewart, K., Ritchie, D. L., Mabbott, N. A., Williams, A., Fraser, H., Morrison, W. I. & Bruce, M. E. ( 1999; ). Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nat Med 5, 1308–1312.[CrossRef]
    [Google Scholar]
  11. Bruce, M. E., Brown, K. L., Mabbott, N. A., Farquhar, C. F. & Jeffrey, M. ( 2000; ). Follicular dendritic cells in TSE pathogenesis. Immunol Today 21, 442–446.[CrossRef]
    [Google Scholar]
  12. Ciriaco, E., Ricci, A., Bronzetti, E., Mammola, C. L., Germanà, G. & Vega, J. A. ( 1995; ). Age-related changes of the noradrenergic and acetylcholinesterase reactive nerve fibres innervating the pigeon bursa of Fabricius. Anat Anz 177, 237–242.[CrossRef]
    [Google Scholar]
  13. Costa, M., Furness, J. B. & Llewellyn-Smith, I. J. ( 1987; ). Histochemistry of the enteric nervous system. In Physiology of the Gastrointestinal Tract, pp. 1–39. Edited by L. R. Jonson, J. Christensen, M. J. Jackson, E. D. Jacobson & J. H. Walsh. New York: Raven Press.
  14. Fehér, E., Fodor, M. & Burnstock, G. ( 1992; ). Distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches. Gut 33, 1195–1198.[CrossRef]
    [Google Scholar]
  15. Felten, D. L. & Felten, S. Y. ( 1988; ). Sympathetic noradrenergic innervation of immune organs. Brain Behav Immun 2, 293–300.[CrossRef]
    [Google Scholar]
  16. Felten, D. L., Felten, S. Y., Carlson, S. L., Olschowka, J. A. & Livnat, S. ( 1985; ). Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 135 (Suppl. 2), 755S–765S.
    [Google Scholar]
  17. Felten, D. L., Felten, S. Y., Bellinger, D. L., Carlson, S. L., Ackerman, K. D., Madden, K. S., Olschowka, J. A. & Livnat, S. ( 1987; ). Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev 100, 225–260.[CrossRef]
    [Google Scholar]
  18. Furness, J. B. & Costa, M. ( 1980; ). Commentary: types of nerves in the enteric nervous system. Neuroscience 5, 1–20.[CrossRef]
    [Google Scholar]
  19. Glatzel, M. & Aguzzi, A. ( 2000; ). Peripheral pathogenesis of prion diseases. Microbes Infect 2, 613–619.[CrossRef]
    [Google Scholar]
  20. Glatzel, M., Klein, M. A., Brander, S. & Aguzzi, A. ( 2000; ). Prions: from neurografts to neuroinvasion. Arch Virol Suppl 16, 3–12.
    [Google Scholar]
  21. Glatzel, M., Heppner, F. L., Albers, K. M. & Aguzzi, A. ( 2001; ). Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron 31, 25–34.[CrossRef]
    [Google Scholar]
  22. Griebel, P. J. & Hein, W. R. ( 1996; ). Expanding the role of Peyer's patches in B-cell ontogeny. Immunol Today 17, 30–39.[CrossRef]
    [Google Scholar]
  23. Groschup, M. H., Weiland, F., Straub, O. C. & Pfaff, E. ( 1996; ). Detection of scrapie agent in the peripheral nervous system of a diseased sheep. Neurobiol Dis 3, 191–195.[CrossRef]
    [Google Scholar]
  24. Hamzeh, H., Gaudillere, A., Sabido, O., Tchou, I., Lambert, C., Schmitt, D., Genin, C. & Misery, L. ( 2000; ). Expression of PGP9.5 on Langerhans' cells and their precursors. Acta Derm Venereol 80, 14–16.
    [Google Scholar]
  25. Hardt, M., Baron, T. & Groschup, M. H. ( 2000; ). A comparative study of immunohistochemical methods for detecting abnormal prion protein with monoclonal and polyclonal antibodies. J Comp Pathol 122, 43–53.[CrossRef]
    [Google Scholar]
  26. Haritani, M., Spencer, Y. I. & Wells, G. A. ( 1994; ). Hydrated autoclave pretreatment enhancement of prion protein immunoreactivity in formalin-fixed bovine spongiform encephalopathy-affected brain. Acta Neuropathol 87, 86–90.[CrossRef]
    [Google Scholar]
  27. Heggebø, R., Press, C. McL., Gunnes, G., Lie, K. I., Tranulis, M. A., Ulvund, M., Groschup, M. H. & Landsverk, T. ( 2000; ). Distribution of prion protein in the ileal Peyer's patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 81, 2327–2337.
    [Google Scholar]
  28. Heggebø, R., Press, C. McL., Gunnes, G., González, L. & Jeffrey, M. ( 2002; ). Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 83, 479–489.
    [Google Scholar]
  29. Hunter, N., Moore, L., Hosie, B. D., Dingwall, W. S. & Greig, A. ( 1997; ). Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Vet Rec 140, 59–63.[CrossRef]
    [Google Scholar]
  30. Ichikawa, S., Sreedharan, S. P., Goetzl, E. J. & Owen, R. L. ( 1994; ). Immunohistochemical localization of peptidergic nerve fibers and neuropeptide receptors in Peyer's patches of the cat ileum. Regul Pept 54, 385–395.[CrossRef]
    [Google Scholar]
  31. Jeffrey, M., Martin, S., Thomson, J. R., Dingwall, W. S., Begara-McGorum, I. & González, L. ( 2001a; ). Onset and distribution of tissue PrP accumulation in scrapie-affected Suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies. J Comp Pathol 125, 48–57.[CrossRef]
    [Google Scholar]
  32. Jeffrey, M., Ryder, S. J., Martin, S., Hawkins, S. A. C., Terry, L., Berthelin-Baker, C. & Bellworthy, S. J. ( 2001b; ). Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). I. Onset and distribution of disease-specific PrP accumulation in brain and viscera. J Comp Pathol 124, 280–289.[CrossRef]
    [Google Scholar]
  33. Kimberlin, R. H., Hall, S. M. & Walker, C. A. ( 1983; ). Pathogenesis of mouse scrapie. Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. J Neurol Sci 61, 315–325.[CrossRef]
    [Google Scholar]
  34. Kitamoto, T., Muramoto, T., Mohri, S., Doh-Ura, K. & Tateishi, J. ( 1991; ). Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt–Jakob disease. J Virol 65, 6292–6295.
    [Google Scholar]
  35. Krammer, H.-J. & Kühnel, W. ( 1993; ). Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. Cell Tissue Res 272, 267–272.[CrossRef]
    [Google Scholar]
  36. Kulkarni-Narla, A., Beitz, A. J. & Brown, D. R. ( 1999; ). Catecholaminergic, cholinergic and peptidergic innervation of gut-associated lymphoid tissue in porcine jejunum and ileum. Cell Tissue Res 298, 275–286.[CrossRef]
    [Google Scholar]
  37. Langlois, N. E., King, G., Herriot, R. & Thompson, W. D. ( 1994; ). Non-enzymatic retrieval of antigen permits staining of follicle centre cells by the rabbit polyclonal antibody to protein gene product 9. 5. J Pathol 173, 249–253.[CrossRef]
    [Google Scholar]
  38. Langlois, N. E., King, G., Herriot, R. & Thompson, W. D. ( 1995; ). An evaluation of the staining of lymphomas and normal tissues by the rabbit polyclonal antibody to protein gene product 9.5 following non-enzymatic retrieval of antigen. J Pathol 175, 433–439.[CrossRef]
    [Google Scholar]
  39. Lasmézas, C. I., Cesbron, J. Y., Deslys, J. P., Demaimay, R., Adjou, K. T., Rioux, R., Lemarie, C., Locht, C. & Dormont, D. ( 1996; ). Immune system-dependent and -independent replication of the scrapie agent. J Virol 70, 1292–1295.
    [Google Scholar]
  40. Lorton, D., Bellinger, D. L., Felten, S. Y. & Felten, D. L. ( 1991; ). Substance P innervation of spleen in rats: nerve fibers associated with lymphocytes and macrophages in specific compartments of the spleen. Brain Behav Immun 5, 29–40.[CrossRef]
    [Google Scholar]
  41. Madden, K. S., Thyagarajan, S. & Felten, D. L. ( 1998; ). Alterations in sympathetic noradrenergic innervation in lymphoid organs with age. Ann N Y Acad Sci 840, 262–268.[CrossRef]
    [Google Scholar]
  42. Maignien, T., Lasmézas, C. I., Beringue, V., Dormont, D. & Deslys, J. P. ( 1999; ). Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. J Gen Virol 80, 3035–3042.
    [Google Scholar]
  43. McBride, P. A., Eikelenboom, P., Kraal, G., Fraser, H. & Bruce, M. E. ( 1992; ). PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol 168, 413–418.[CrossRef]
    [Google Scholar]
  44. McBride, P. A., Schulz-Schaeffer, W. J., Donaldson, M., Bruce, M. E., Diringer, H., Kretzschmar, H. A. & Beekes, M. ( 2001; ). Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75, 9320–9327.[CrossRef]
    [Google Scholar]
  45. Pfoch, M. & Unsicker, K. ( 1972; ). Electron microscopic study on the innervation of Peyer's patches of the Syrian hamster. Z Zellforsch Mikrosk Anat 123, 425–429.[CrossRef]
    [Google Scholar]
  46. Prusiner, S. B. ( 1982; ). Novel proteinaceous infectious particles cause scrapie. Science 216, 136–144.[CrossRef]
    [Google Scholar]
  47. Race, R., Oldstone, M. & Chesebro, B. ( 2000; ). Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: role of prion protein expression in peripheral nerves and spleen. J Virol 74, 828–833.[CrossRef]
    [Google Scholar]
  48. Reynolds, J. D. & Morris, B. ( 1983; ). The evolution and involution of Peyer's patches in foetal and postnatal sheep. Eur J Immunol 13, 627–635.[CrossRef]
    [Google Scholar]
  49. Taraboulos, A., Jendroska, K., Serban, D., Yang, S. L., DeArmond, S. J. & Prusiner, S. B. ( 1992; ). Regional mapping of prion proteins in brain. Proc Natl Acad Sci U S A 89, 7620–7624.[CrossRef]
    [Google Scholar]
  50. Timmermans, J.-P., Scheuermann, D. W., Stach, W., Adriaensen, D. & De Groodt-Lasseel, M. H. A. ( 1992; ). Functional morphology of the enteric nervous system with special reference to large mammals. Eur J Morphol 30, 113–122.
    [Google Scholar]
  51. van Keulen, L. J., Schreuder, B. E., Meloen, R. H., Mooij-Harkes, G., Vromans, M. E. & Langeveld, J. P. ( 1996; ). Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34, 1228–1231.
    [Google Scholar]
  52. van Keulen, L. J., Schreuder, B. E., Vromans, M. E., Langeveld, J. P. & Smits, M. A. ( 1999; ). Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie. J Comp Pathol 121, 55–63.[CrossRef]
    [Google Scholar]
  53. van Keulen, L. J., Schreuder, B. E., Vromans, M. E., Langeveld, J. P. & Smits, M. A. ( 2000; ). Pathogenesis of natural scrapie in sheep. Arch Virol Suppl 16, 57–71.
    [Google Scholar]
  54. Westaway, D., Zuliani, V., Cooper, C. M., Da Costa, M., Neuman, S., Jenny, A. L., Detwiler, L. & Prusiner, S. B. ( 1994; ). Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 8, 959–969.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.18874-0
Loading
/content/journal/jgv/10.1099/vir.0.18874-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error