NR AXYG
AU Villiers,C.; Papaioannou,A.; Candeias,S.; Aude-Garcia,C.; Marche,P.
TI Mouse Dendritic Cells and PrPc Synthesis
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.23
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Dendritic cells (DCs) reside at the interface between innate and adaptive immunity, they are known for their antigen-presenting capacity and their role in primary specific immune responses. via pathogen recognition receptors, they detect and then internalize and process foreign molecules for antigen presentation, they participate also in the first steps of propagation of PrPsc in animals.
As amplification of PrPsc requires the presence of PrPc, we investigated the ability of DC to synthesize PrPc. DCs were derived from bone marrow progenitors and PrPc expression was analyzed. Progenitors as well as immature cells did not synthesize PrPc whereas mature DCs expressed PrPc at their surface. DCs activation was induced by various molecules such as IFng, anti CD40 or ligands of TLR, in each case, the activation was checked by the increase expression of Class II molecules and the secretion of various cytokines (IL12, IL6, TNF). DC activation induced also the expression of PrPc at a similar level that was observed on mature DCs. Whatever the activators, PrPc expression was the same; this was confirmed by the quantification of PrPc RNA.
As shown by confocal microscopy: PrPc was localized on lipids raft as revealed by its co-localisation with specific markers of these membrane domains (cholera toxin). No PrPc was observed in the intracellular vesicles indicating the absence of internalization of PrPc even after crosslinking using anti-PrPc antibodies.
As PrPc was previously shown to bind cupper and to interfere with the RedOx balance of the cells. We compared DC from various mouse strains (PrP-KO and TgA20 witch over express PrPc): no difference was observed between these DC when we considered their RedOx and their growth capacity. Furthermore, using a model of inflammation induce by irradiation, we have measured the accumulation of DC to specific localization, neither the speed of cell response, nor the amount of cells accumulated were influenced by the absence or the over expression of PrPc. All our results indicate that the synthesis of PrPc by DC is clearly up-regulated by the cellular activation but the various DC function tested were not influenced by the presence or not of PrPc. Further analysis will be carried out to check a potential role of PrPc in the mechanism of antigen presentation and induction of T cell response. This work is supported by the EC program FOOD-2004-T5.4.5.3 number 23144
AD C. Villiers, A. Papaioannou, P. Marche, Inserm U823, France; S. Candeias, C. Aude-Garcia, Cnrs Umr, Bbsi/iRSTV/Cea, France
SP englisch
PO Schottland