NR AWMK
AU Reissinger,A.; Hammann,J.; Löwer,J.; Montrasio,F.
TI Antigen presenting cells fail to mature after in vitro exposure to the scrapie agent but stop scrapie agent degradation after TLR ligand-induced activation
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-44
PT Konferenz-Poster
AB Following oral uptake of the scrapie agent (PrPsc) in mice, neuroinvasion occurs after a first phase of prion accumulation and replication in lymphoid organs such as the draining lymph nodes and Peyer's Patches. How the agent reaches respective sites of accumulation and if cellular and/or acellular components are involved in this process is under intense investigation. Since antigen presenting cells (APCs) are the sentinels of the immune system and migrate from peripheral sites to the draining lymph nodes (and therefore might carry infectivity as their cargo), the aim of our study was to analyze in vitro the role of APCs in PrPsc (RML strain) degradation and how degradation is affected by co-stimulation of APCs with several danger signals. We also investigated whether PrPsc itself represents a danger signal to bone-marrow derived dendritic cells (BMDCs) leading to an altered activation state that could ultimately contribute to the induction of tolerance to the prion protein. We found that both macrophages and BMDCs degrade PrPsc but stop degradation after Toll-like receptor (TLR) ligand-induced activation. Using several activation markers (I-Ab, H-1Kb, CD86, CD80) we could neither show any phenotypic change of BMDCs after exposure to PrPsc, nor altered activation by co-stimulation with TLR ligands indicating that BMDCs do not perceive the scrapie agent as a danger signal - or become attenuated by PrPsc. However, our data on reduced degradation of PrPsc after TLR ligand-induced activation indicate that inflammatory processes and/or co-infections during scrapie pathogenesis might enhance prion pathogenesis by impeding PrPsc breakdown by APCs.
AD Paul-Ehrlich-Institute, Prion Research Group, Langen, Germany. E-mail: reian@pei.de
SP englisch
PO Italien