1887

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Volume 87, Issue 11

Lymphoid follicles of the ileal Peyer's patch of lambs express low levels of PrP, as demonstrated by quantitative real-time RT-PCR on microdissected tissue compartments, hybridization and immunohistochemistry Free

Abstract

The expression level of normal cellular prion protein (PrP) is thought to influence the transmission of transmissible spongiform encephalopathies (TSEs) from the peripheral entry site to the site of pathological changes in the central nervous system. In many TSEs, the clinical disease is preceded by a period in which the agent accumulates in lymphoid organs, particularly in association with follicular dendritic cells of lymphoid follicles. As the probable route of entry of the TSE agent is via the gut, the expression profile of PrP was examined in well-developed gut-associated lymphoid tissue of lambs, the ileal Peyer's patch, by laser microdissection and real-time RT-PCR. Lymphoid follicles were found to have very low levels of expression, whilst highest levels were detected in the outer submucosa and the muscular layer. These findings were supported by hybridization and immunohistochemistry, which showed specific labelling in nerve cells in ganglia of the submucosal (Meissner's) and myenteric (Auerbach's) plexi of the enteric nervous system. Based on the assumption that potential sites for conversion to the scrapie-related prion protein (PrP) should display high levels of expression of PrP, this study suggests that the accumulation of PrP in the lymphoid follicles of the Peyer's patch is not preceded by PrP conversion in the same tissue compartment.

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2006-11-01
2024-04-20
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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. Barthel L. K., Raymond P. A. 1993; Subcellular localization of alpha-tubulin and opsin mRNA in the goldfish retina using digoxigenin-labeled cRNA probes detected by alkaline phosphatase and HRP histochemistry. J Neurosci Methods 50:145–152 [CrossRef]
     [Google Scholar]
  3. Blättler T., Brandner S., Raeber A. J., Klein M. A., Voigtländer T., Weissmann C., Aguzzi A. 1997; PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 389:69–73 [CrossRef]
     [Google Scholar]
  4. Brandner S., Raeber A., Sailer A., Blättler T., Fischer M., Weissmann C., Aguzzi A. 1996; Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system. Proc Natl Acad Sci U S A 93:13148–13151 [CrossRef]
     [Google Scholar]
  5. Brown H. R., Goller N. L., Rudelli R. D., Merz G. S., Wolfe G. C., Wisniewski H. M., Robakis N. K. 1990; The mRNA encoding the scrapie agent protein is present in a variety of non-neuronal cells. Acta Neuropathol 80:1–6 [CrossRef]
     [Google Scholar]
  6. 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]
  7. 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]
  8. Burthem J., Urban B., Pain A., Roberts D. J. 2001; The normal cellular prion protein is strongly expressed by myeloid dendritic cells. Blood 98:3733–3738 [CrossRef]
     [Google Scholar]
  9. Cagampang F. R. A., Whatley S. A., Mitchell A. L., Powell J. F., Campbell I. C., Coen C. W. 1999; Circadian regulation of prion protein messenger RNA in the rat forebrain: a widespread and synchronous rhythm. Neuroscience 91:1201–1204 [CrossRef]
     [Google Scholar]
  10. Caughey B., Race R. E., Chesebro B. 1988; Detection of prion protein mRNA in normal and scrapie-infected tissues and cell lines. J Gen Virol 69:711–716 [CrossRef]
     [Google Scholar]
  11. Caughey B., Raymond G. J., Callahan M. A., Wong C., Baron G. S., Xiong L. W. 2001; Interactions and conversions of prion protein isoforms. Adv Protein Chem 57:139–169
     [Google Scholar]
  12. Defaweux V., Dorban G., Demonceau C., Piret J., Jolois O., Thellin O., Thielen C., Heinen E., Antoine N. 2005; Interfaces between dendritic cells, other immune cells, and nerve fibres in mouse Peyer's patches: potential sites for neuroinvasion in prion diseases. Microsc Res Tech 66:1–9 [CrossRef]
     [Google Scholar]
  13. Elsen J.-M., Amigues Y., Schelcher F. & 7 other authors 1999; Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445 [CrossRef]
     [Google Scholar]
  14. Ford M. J., Burton L. J., Li H., Graham C. H., Frobert Y., Grassi J., Hall S. M., Morris R. J. 2002a; A marked disparity between the expression of prion protein and its message by neurones of the CNS. Neuroscience 111:533–551 [CrossRef]
     [Google Scholar]
  15. Ford M. J., Burton L. J., Morris R. J., Hall S. M. 2002b; Selective expression of prion protein in peripheral tissues of the adult mouse. Neuroscience 113:177–192 [CrossRef]
     [Google Scholar]
  16. Foss D. L., Baarsch M. J., Murtaugh M. P. 1998; Regulation of hypoxanthine phosphoribosyltransferase, glyceraldehyde-3-phosphate dehydrogenase and beta-actin mRNA expression in porcine immune cells and tissues. Anim Biotechnol 9:67–78 [CrossRef]
     [Google Scholar]
  17. Garcia-Crespo D., Juste R. A., Hurtado A. 2005; Selection of ovine housekeeping genes for normalisation by real-time RT-PCR; analysis of PrP gene expression and genetic susceptibility to scrapie. BMC Vet Res 1:3 [CrossRef]
     [Google Scholar]
  18. Gerber H. A., Morris B., Trevella W. 1986; The role of gut-associated lymphoid tissues in the generation of immunoglobulin-bearing lymphocytes in sheep. Aust J Exp Biol Med Sci 64:201–213 [CrossRef]
     [Google Scholar]
  19. Ghosh S. 2004; Mechanism of intestinal entry of infectious prion protein in the pathogenesis of variant Creutzfeldt–Jakob disease. Adv Drug Deliv Rev 56:915–920 [CrossRef]
     [Google Scholar]
  20. Glatzel M., Aguzzi A. 2000; PrPC expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol 81:2813–2821
     [Google Scholar]
  21. González L., Martin S., Houston F. E., Hunter N., Reid H. W., Bellworthy S. J., Jeffrey M. 2005; Phenotype of disease-associated PrP accumulation in the brain of bovine spongiform encephalopathy experimentally infected sheep. J Gen Virol 86:827–838 [CrossRef]
     [Google Scholar]
  22. Hadlow W. J., Kennedy R. C., Race R. E. 1982; Natural infection of Suffolk sheep with scrapie virus. J Infect Dis 146:657–664 [CrossRef]
     [Google Scholar]
  23. Halleraker M., Landsverk T., Nicander L. 1990; Organization of ruminant Peyer's patches as seen with enzyme histochemical markers of stromal and accessory cells. Vet Immunol Immunopathol 26:93–104 [CrossRef]
     [Google Scholar]
  24. 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]
  25. 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]
  26. Heggebø R., Press C. McL., Gunnes G., Ulvund M. J., Tranulis M. A., Landsverk T. 2003a; Detection of PrPSc in lymphoid tissues of lambs experimentally exposed to the scrapie agent. J Comp Pathol 128:172–181 [CrossRef]
     [Google Scholar]
  27. Heggebø R., González L., Press C. McL., Gunnes G., Espenes A., Jeffrey M. 2003b; Disease-associated PrP in the enteric nervous system of scrapie-affected Suffolk sheep. J Gen Virol 84:1327–1338 [CrossRef]
     [Google Scholar]
  28. Heppner F. L., Christ A. D., Klein M. A., Prinz M., Fried M., Kraehenbuhl J.-P., Aguzzi A. 2001; Transepithelial prion transport by M cells. Nat Med 7:976–977 [CrossRef]
     [Google Scholar]
  29. Huang F.-P., MacPherson G. G. 2004; Dendritic cells and oral transmission of prion diseases. Adv Drug Deliv Rev 56:901–913 [CrossRef]
     [Google Scholar]
  30. Huang F.-P., Farquhar C. F., Mabbott N. A., Bruce M. E., MacPherson G. G. 2002; Migrating intestinal dendritic cells transport PrPSc from the gut. J Gen Virol 83:267–271
     [Google Scholar]
  31. Jeffrey M., McGovern G., Goodsir C. M., Brown K. L., Bruce M. E. 2000; Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy. J Pathol 191:323–332 [CrossRef]
     [Google Scholar]
  32. Kelsall B. L., Strober W. 1996; Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch. J Exp Med 183:237–247 [CrossRef]
     [Google Scholar]
  33. Kimberlin R. H., Walker C. A. 1989; Pathogenesis of scrapie in mice after intragastric infection. Virus Res 12:213–220 [CrossRef]
     [Google Scholar]
  34. Kubosaki A., Ueno A., Matsumoto Y., Doi K., Saeki K., Onodera T. 2000; Analysis of prion protein mRNA by in situ hybridization in brain and placenta of sheep. Biochem Biophys Res Commun 273:890–893 [CrossRef]
     [Google Scholar]
  35. Landsverk T., Halleraker M., Aleksandersen M., McClure S., Hein W., Nicander L. 1991; The intestinal habitat for organized lymphoid tissues in ruminants; comparative aspects of structure, function and development. Vet Immunol Immunopathol 28:1–16 [CrossRef]
     [Google Scholar]
  36. Lezmi S., Bencsik A., Baron T. 2001; CNA42 monoclonal antibody identifies FDC as PrPsc accumulating cells in the spleen of scrapie affected sheep. Vet Immunol Immunopathol 82:1–8 [CrossRef]
     [Google Scholar]
  37. Lucier M. R., Thompson R. E., Waire J., Lin A. W., Osborne B. A., Goldsby R. A. 1998; Multiple sites of V λ diversification in cattle. J Immunol 161:5438–5444
     [Google Scholar]
  38. Mabbott N. A., Williams A., Farquhar C. F., Pasparakis M., Kollias G., Bruce M. E. 2000; Tumor necrosis factor alpha-deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie. J Virol 74:3338–3344 [CrossRef]
     [Google Scholar]
  39. Mabbott N. A., Bruce M. E., Botto M., Walport M. J., Pepys M. B. 2001; Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med 7:485–487 [CrossRef]
     [Google Scholar]
  40. Marcos Z., Pffeifer K., Bodegas M. E., Sesma M. P., Guembe L. 2004; Cellular prion protein is expressed in a subset of neuroendocrine cells of the rat gastrointestinal tract. J Histochem Cytochem 52:1357–1365 [CrossRef]
     [Google Scholar]
  41. 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]
  42. McLennan N. F., Rennison K. A., Bell J. E., Ironside J. W. 2001; In situ hybridization analysis of PrP mRNA in human CNS tissues. Neuropathol Appl Neurobiol 27:373–383 [CrossRef]
     [Google Scholar]
  43. Müller-Hermelink H. K., Heusermann U., Stutte H. J. 1974; Enzyme histochemical observations on the localization and structure of the T cell and B cell regions in the human spleen. Cell Tissue Res 154:167–179
     [Google Scholar]
  44. Nicander L., Halleraker M., Landsverk T. 1991; Ontogeny of reticular cells in the ileal Peyer's patch of sheep and goats. Am J Anat 191:237–249 [CrossRef]
     [Google Scholar]
  45. Ning Z.-Y., Zhao D.-M., Yang J.-M., Cui Y.-L., Meng L.-P., Wu C.-D., Liu H.-X. 2005; Quantification of prion gene expression in brain and peripheral organs of golden hamster by real-time RT-PCR. Anim Biotechnol 16:55–65 [CrossRef]
     [Google Scholar]
  46. Press C. McL., Halleraker M., Landsverk T. 1992; Ontogeny of leukocyte populations in the ileal Peyer's patch of sheep. Dev Comp Immunol 16:229–241 [CrossRef]
     [Google Scholar]
  47. Press C. McL., Reynolds J. D., McClure S. J., Simpson-Morgan M. W., Landsverk T. 1996; Fetal lambs are depleted of IgM+ cells following a single injection of an anti-IgM antibody early in gestation. Immunology 88:28–34 [CrossRef]
     [Google Scholar]
  48. Prinz M., Montrasio F., Klein M. A., Schwarz P., Priller J., Odermatt B., Pfeffer K., Aguzzi A. 2002; Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. Proc Natl Acad Sci U S A 99:919–924 [CrossRef]
     [Google Scholar]
  49. Prusiner S. B., Scott M. R., DeArmond S. J., Cohen F. E. 1998; Prion protein biology. Cell 93:337–348 [CrossRef]
     [Google Scholar]
  50. Raymond I., Al Saati T., Tkaczuk J., Chittal S., Delsol G. 1997; CNA.42, a new monoclonal antibody directed against a fixative-resistant antigen of follicular dendritic reticulum cells. Am J Pathol 151:1577–1585
     [Google Scholar]
  51. Reynaud C.-A., Mackay C. R., Müller R. G., Weill J.-C. 1991; Somatic generation of diversity in a mammalian primary lymphoid organ: the sheep ileal Peyer's patches. Cell 64:995–1005 [CrossRef]
     [Google Scholar]
  52. Reynolds J. D., Morris B. 1983; The evolution and involution of Peyer's patches in fetal and postnatal sheep. Eur J Immunol 13:627–635 [CrossRef]
     [Google Scholar]
  53. Shlomchik M. J., Radebold K., Duclos N., Manuelidis L. 2001; Neuroinvasion by a Creutzfeldt-Jakob disease agent in the absence of B cells and follicular dendritic cells. Proc Natl Acad Sci U S A 98:9289–9294 [CrossRef]
     [Google Scholar]
  54. St Rose S. G., Hunter N., Matthews L. & 7 other authors 2006; Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies. BMC Infect Dis 6:5 [CrossRef]
     [Google Scholar]
  55. Sugaya M., Nakamura K., Watanabe T. & 12 other authors 2002; Expression of cellular prion-related protein by murine Langerhans cells and keratinocytes. J Dermatol Sci 28:126–134 [CrossRef]
     [Google Scholar]
  56. Thielen C., Mélot F., Jolois O., Leclercq F., Tsunoda R., Frobert Y., Heinen E., Antoine N. 2001; Isolation of bovine follicular dendritic cells allows the demonstration of a particular cellular prion protein. Cell Tissue Res 306:49–55 [CrossRef]
     [Google Scholar]
  57. Tichopad A., Pfaffl M. W., Didier A. 2003; Tissue-specific expression pattern of bovine prion gene: quantification using real-time RT-PCR. Mol Cell Probes 17:5–10 [CrossRef]
     [Google Scholar]
  58. van Keulen L. J. M., Schreuder B. E. C., Vromans M. E. W., Langeveld J. P. M., Smits M. A. 1999; Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie. J Comp Pathol 121:55–63 [CrossRef]
     [Google Scholar]
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Lymphoid follicles of the ileal Peyer's patch of lambs express low levels of PrP, as demonstrated by quantitative real-time RT-PCR on microdissected tissue compartments, in situ hybridization and immunohistochemistry
J. Gen. Virol. 87, 3463 (2006); https://doi.org/10.1099/vir.0.82008-0
/content/journal/jgv/10.1099/vir.0.82008-0
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