Principal Investigators

    Professor NA Mabbott


    University of Edinburgh

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Determining the role of M cells in TSE agent neuroinvasion from the intestine

    Source of funding information


    Total sum awarded (Euro)

    € 440,827

    Start date of award


    Total duration of award in years



    Research Abstract

    After oral exposure many TSE agents replicate first on follicular dendritic cells (FDC) in the gut-associated lymphoid tissues (GALT) as they spread from the site exposure (intestine) to the brain (termed, neuroinvasion). For TSE agents to replicate on FDC in the GALT after ingestion of a contaminated meal they must first cross the gut epithelium. However, the precise cellular mechanism by which TSE agents are conveyed into Peyer’s patches is not known. Within the Peyer’s patch epithelium are M cells, unique epithelial cells specialized for the transepithelial transport of particles. M cells are plausible sites of TSE agent transport across the gut epithelium, but definitive demonstration in vivo is lacking. This is important, as several M cell-independent mechanisms have also been proposed. A thorough understanding of the early stages of TSE pathogenesis in the GALT is crucial to determine the factors that influence the risk of infection and the identification of cellular and molecular targets for intervention. Using unique in vivo models will be used to definitively determine the role of M cells in TSE agent neuroinvasion from the intestine and test the hypothesis that M cells play a crucial role in oral TSE pathogenesis. Objective 1 tests the hypothesis that in the specific absence of M cells, TSE agent accumulation in the GALT is blocked and neuroinvasion impaired. Objective 2 aims to determine whether inflammatory stimuli that enhance M cell differentiation also enhance TSE agent uptake. Objective 3 will determine whether inflammation-mediated villous M cell expansion exacerbates TSE pathogenesis by facilitating systemic dissemination and neuroinvasion from tissues other than Peyer’s patches. These data will help predict how inflammation and co-fection with gastrointestinal pathogens may influence TSE pathogenesis. This study will provide important missing data on how orally-acquired TSE agents infect the GALT during steady-state and inflammatory conditions.

    Further information available at:

Types: Investments < €500k
Member States: United Kingdom
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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