This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mabbott, N. A.
Right arrow Articles by Bruce, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mabbott, N. A.
Right arrow Articles by Bruce, M. E.

 Previous Article  |  Next Article 

Journal of Virology, April 2000, p. 3338-3344, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie

Neil A. Mabbott,1,* Alun Williams,1,dagger Christine F. Farquhar,1 Manolis Pasparakis,2 Giorgos Kollias,2 and Moira E. Bruce1

Neuropathogenesis Unit, Institute for Animal Health, Edinburgh EH9 3JF, Scotland, United Kingdom,1 and Hellenic Pasteur Institute, 115 21 Athens, Greece2

Received 21 October 1999/Accepted 4 January 2000

In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs) of the spleen and lymph nodes are important sites of extraneural replication, from which infection is likely to spread to the CNS along peripheral nerves. Here, using immunodeficient mice, we investigate the identity of the cells in the spleen that are important for disease propagation. Despite possessing functional T and B lymphocytes, tumor necrosis factor alpha-deficient (TNF-alpha -/-) mice lack GCs and follicular dendritic cell (FDC) networks in lymphoid tissues. In contrast, lymphoid tissues of interleukin-6-deficient (IL-6-/-) mice possess FDC networks but have impaired GCs. When the CNSs of TNF-alpha -/-, IL-6-/-, and wild-type mice were directly challenged with the ME7 scrapie strain, 100% of the mice were susceptible, developing disease after closely similar incubation periods. However, when challenged peripherally (intraperitoneally), most TNF-alpha -/- mice failed to develop scrapie up to 503 days postinjection. All wild-type and IL-6-/- mice succumbed to disease approximately 300 days after the peripheral challenge. High levels of scrapie infection and the disease-specific isomer of the prion protein, PrPSc, were detectable in spleens from challenged wild-type and IL-6-/- mice but not from TNF-alpha -/- mice. Histopathological analysis of spleen tissue demonstrated heavy PrP accumulations in direct association with FDCs in challenged wild-type and IL-6-/- mice. No PrPSc accumulation was detected in spleens from TNF-alpha -/- mice. We conclude that, for the ME7 scrapie strain, mature FDCs are critical for replication in lymphoid tissues and that in their absence, neuroinvasion following peripheral challenge is impaired.

* Corresponding author. Mailing address: Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Rd., Edinburgh EH9 3JF, Scotland, United Kingdom. Phone: 44 131 667 5204. Fax: 44 131 668 3872. E-mail: neil.mabbott{at}bbsrc.ac.uk.

dagger Present address: Department of Veterinary Pathology, Glasgow University Veterinary School, Glasgow G61 1QH, Scotland, United Kingdom.

Journal of Virology, April 2000, p. 3338-3344, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tribouillard-Tanvier, D., Striebel, J. F., Peterson, K. E., Chesebro, B. (2009). Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels. J. Virol. 83: 11244-11253 [Abstract] [Full Text]  
  • Brown, K. L., Wathne, G. J., Sales, J., Bruce, M. E., Mabbott, N. A. (2009). The Effects of Host Age on Follicular Dendritic Cell Status Dramatically Impair Scrapie Agent Neuroinvasion in Aged Mice. J. Immunol. 183: 5199-5207 [Abstract] [Full Text]  
  • Bessen, R. A., Martinka, S., Kelly, J., Gonzalez, D. (2009). Role of the Lymphoreticular System in Prion Neuroinvasion from the Oral and Nasal Mucosa. J. Virol. 83: 6435-6445 [Abstract] [Full Text]  
  • Tamguney, G., Giles, K., Glidden, D. V., Lessard, P., Wille, H., Tremblay, P., Groth, D. F., Yehiely, F., Korth, C., Moore, R. C., Tatzelt, J., Rubinstein, E., Boucheix, C., Yang, X., Stanley, P., Lisanti, M. P., Dwek, R. A., Rudd, P. M., Moskovitz, J., Epstein, C. J., Cruz, T. D., Kuziel, W. A., Maeda, N., Sap, J., Ashe, K. H., Carlson, G. A., Tesseur, I., Wyss-Coray, T., Mucke, L., Weisgraber, K. H., Mahley, R. W., Cohen, F. E., Prusiner, S. B. (2008). Genes contributing to prion pathogenesis. J. Gen. Virol. 89: 1777-1788 [Abstract] [Full Text]  
  • Raymond, C. R., Aucouturier, P., Mabbott, N. A. (2007). In Vivo Depletion of CD11c+ Cells Impairs Scrapie Agent Neuroinvasion from the Intestine. J. Immunol. 179: 7758-7766 [Abstract] [Full Text]  
  • Zabel, M. D., Heikenwalder, M., Prinz, M., Arrighi, I., Schwarz, P., Kranich, J., von Teichman, A., Haas, K. M., Zeller, N., Tedder, T. F., Weis, J. H., Aguzzi, A. (2007). Stromal Complement Receptor CD21/35 Facilitates Lymphoid Prion Colonization and Pathogenesis. J. Immunol. 179: 6144-6152 [Abstract] [Full Text]  
  • Glaysher, B. R., Mabbott, N. A. (2007). Role of the GALT in Scrapie Agent Neuroinvasion from the Intestine. J. Immunol. 178: 3757-3766 [Abstract] [Full Text]  
  • Austbo, L., Espenes, A., Olsaker, I., Press, C. McL., Skretting, G. (2006). 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: 3463-3471 [Abstract] [Full Text]  
  • Trevitt, C. R, Collinge, J. (2006). A systematic review of prion therapeutics in experimental models. Brain 129: 2241-2265 [Abstract] [Full Text]  
  • Ierna, M., Farquhar, C. F., Outram, G. W., Bruce, M. E. (2006). Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen. J. Virol. 80: 474-482 [Abstract] [Full Text]  
  • Bartz, J. C., DeJoia, C., Tucker, T., Kincaid, A. E., Bessen, R. A. (2005). Extraneural Prion Neuroinvasion without Lymphoreticular System Infection. J. Virol. 79: 11858-11863 [Abstract] [Full Text]  
  • Cunningham, C., Wilcockson, D. C., Boche, D., Perry, V. H. (2005). Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease. J. Virol. 79: 5174-5184 [Abstract] [Full Text]  
  • Mohan, J., Bruce, M. E., Mabbott, N. A. (2005). Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells. J. Virol. 79: 1888-1897 [Abstract] [Full Text]  
  • Thackray, A. M., McKenzie, A. N., Klein, M. A., Lauder, A., Bujdoso, R. (2004). Accelerated Prion Disease in the Absence of Interleukin-10. J. Virol. 78: 13697-13707 [Abstract] [Full Text]  
  • Schultz, J., Schwarz, A., Neidhold, S., Burwinkel, M., Riemer, C., Simon, D., Kopf, M., Otto, M., Baier, M. (2004). Role of Interleukin-1 in Prion Disease-Associated Astrocyte Activation. Am. J. Pathol. 165: 671-678 [Abstract] [Full Text]  
  • Brown, A. R., Webb, J., Rebus, S., Walker, R., Williams, A., Fazakerley, J. K. (2003). Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease. J. Gen. Virol. 84: 2605-2611 [Abstract] [Full Text]  
  • Mabbott, N. A., Young, J., McConnell, I., Bruce, M. E. (2003). Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility. J. Virol. 77: 6845-6854 [Abstract] [Full Text]  
  • Prinz, M., Huber, G., Macpherson, A. J. S., Heppner, F. L., Glatzel, M., Eugster, H.-P., Wagner, N., Aguzzi, A. (2003). Oral Prion Infection Requires Normal Numbers of Peyer's Patches but Not of Enteric Lymphocytes. Am. J. Pathol. 162: 1103-1111 [Abstract] [Full Text]  
  • Luhr, K. M., Wallin, R. P. A., Ljunggren, H.-G., Low, P., Taraboulos, A., Kristensson, K. (2002). Processing and Degradation of Exogenous Prion Protein by CD11c+ Myeloid Dendritic Cells In Vitro. J. Virol. 76: 12259-12264 [Abstract] [Full Text]  
  • Mabbott, N. A., McGovern, G., Jeffrey, M., Bruce, M. E. (2002). Temporary Blockade of the Tumor Necrosis Factor Receptor Signaling Pathway Impedes the Spread of Scrapie to the Brain. J. Virol. 76: 5131-5139 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Mabbott, N. A., Bruce, M. E. (2001). The immunobiology of TSE diseases. J. Gen. Virol. 82: 2307-2318 [Full Text]  
  • Kaeser, P. S., Klein, M. A., Schwarz, P., Aguzzi, A. (2001). Efficient Lymphoreticular Prion Propagation Requires PrPc in Stromal and Hematopoietic Cells. J. Virol. 75: 7097-7106 [Abstract] [Full Text]  
  • 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. USA 99: 919-924 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»