The role of CXCR5 expressing dendritic cells in transmissible spongiform encephalopathy pathogenesis

Barry Bradford, Andreas Lengeling, David Sester, Neil Mabbott

Research output: Contribution to conferenceAbstractpeer-review

Abstract / Description of output

Following oral exposure transmissible spongiform encephalopathy (TSE) agents often accumulate first upon follicular dendritic cells (FDC) in the gut-associated lymphoid tissues before spreading to the nervous system. During the initial stage of oral infection with TSE, conventional dendritic cells (cDC) are considered to be key candidates for the transport of the infectious agent from the gut epithelium to FDC. Transgenic depletion of CD11c+ cells (cDC) at the point of experimental TSE infection drastically reduced susceptibility to disease. cDC are professional antigen-presenting cells able to initiate innate and adaptive immune responses against invading pathogens. Following uptake of antigen, cDC migrate towards local lymphoid tissues to present antigen to effector cells. This process is dependent upon the expression of chemokine receptors by cDC. FDC produce high levels of CXCL13, this chemokine attracts CXCR5-expressing B cells to FDC, forming B-cell follicles. A subset of cDC has also been shown to express CXCR5 and migrate into B-cell follicles.

This project aims to test the hypothesis that following oral TSE exposure CXCR5-expressing cDC acquire TSE agents and deliver them to FDC. Utilising a Cre/Lox transgenic mouse model that will experience CXCR5 gene-deletion only in CD11c+ cells, the effects of CXCR5-knockout in cDC will be studied. This project will focus on the effects on cDC function, lymphoid organogenesis, impact upon innate and adaptive immune systems, and oral TSE pathogenesis.
Original languageEnglish
Publication statusPublished - 3 Jun 2015
EventEdinburgh Immunology Group Summer Symposium 2015 - Playfair Library Hall, Old College, Edinburgh, United Kingdom
Duration: 3 Jun 2015 → …

Symposium

SymposiumEdinburgh Immunology Group Summer Symposium 2015
Country/TerritoryUnited Kingdom
CityEdinburgh
Period3/06/15 → …

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