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The role of the immune system in TSE agent neuroinvasion

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Summary

Many natural infections with transmissible spongiform encephalopathy (TSE) agents are likely to be acquired peripherally for example, following ingestion of contaminated feed. Following peripheral exposure TSE agents accumulate in lymphoid tissues before spreading to the brain. Many studies have attempted to identify the cells and their components that are required for the delivery of the TSE agent from the site of inoculation to the brain, a process termed neuroinvasion. In the lymphoid tissues of TSE-affected hosts these agents, as identified by disease-specific prion protein accumulations, usually accumulate on follicular dendritic cells (FDCs). Studies of mouse TSE models have shown that mature FDCs are critical for replication of infection in lymphoid tissues and subsequent neuroinvasion. Although examples of FDC-independent neuroinvasion have been described, treatments that interfere with the integrity or function of FDCs reduce TSE susceptibility by blocking the spread of disease to the brain. For example, temporary depletion of FDCs before oral inoculation with TSE agents blocks the accumulation of disease-specific PrP in Peyer’s patches and mesenteric lymph nodes, and prevents neuroinvasion.

Studies in mice have shown that skin scarification is also an effective means of TSE agent transmission. Following inoculation via the skin the agent accumulates in the draining lymph node in association with FDCs. The accumulation of TSE agents in association with FDCs is also critical for the transmission of disease from the skin to the brain, as disease susceptibility is reduced in their absence. The mechanisms through which TSE agents are transported from the site of inoculation such as the gut or skin to lymphoid tissues are not known. Bone marrow-derived migratory dendritic cells have been proposed as a potential method of TSE agent transport from the gut lumen. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen, suggesting these cells might play a role in TSE agent transportation from the skin. To investigate the potential role of LCs in TSE agent transportation, mouse models have been utilized in which their migration was blocked. Experiments show that the early accumulation of TSE agents in the draining lymph node and their subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus although LCs have the potential to acquire TSE agents they are not involved in their transportation to draining lymphoid tissues.

The identification of cell populations critical for TSE pathogenesis provides cellular targets to which therapies can be directed. Described below are current understandings of the involvement of the immune system in the neuroinvasion of TSE agents.

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Authors and Affiliations

  1. Institute for Animal Health, Ogston Building West Mains Road, Edinburgh, EH9 3JF, UK

    Neil A. Mabbott, Joanne Mohan & Moira E. Bruce

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  1. Neil A. Mabbott
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  2. Joanne Mohan
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  3. Moira E. Bruce
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Editors and Affiliations

  1. Department of Prion Research, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Tetsuyuki Kitamoto M.D.

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© 2005 Springer-Verlag Tokyo

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Mabbott, N.A., Mohan, J., Bruce, M.E. (2005). The role of the immune system in TSE agent neuroinvasion. In: Kitamoto, T. (eds) Prions. Springer, Tokyo. https://doi.org/10.1007/4-431-29402-3_10

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  • DOI: https://doi.org/10.1007/4-431-29402-3_10

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-25539-0

  • Online ISBN: 978-4-431-29402-3

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