Cellular pathogenesis of prion diseases

• Research unit: EU RFP
• Project number: 98.0201

Key words (English)

Prions; prion disease; immune system; follicular dendritic cells; therapy

Alternative project number (English)

EU project number: BMH4CT98-3265

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Short description (English)

See abstract

Partners and International Organizations (English)

Coordinator: Universität Göttingen (D)

Abstract (English)

Efficient lymphoreticular prion propagation requires PrPC in stromal and hematopoietic cellsIn most prion diseases, infectivity accumulates in lymphoreticular organs early after infection. Defects in hematopoietic compartments, such as impaired B cell maturation, or in stromal compartments, such as abrogation of follicular dendritic cells (FDCs), can delay or prevent lymphoreticular prion colonization. However, the nature of the compartment in which prion replication takes place is controversial, and it is unclear whether this compartment coincides with that expressing the normal prion protein (PrPC). Here we studied the distribution of infectivity in splenic fractions of wild-type mice, mice deficent in FDCs and fetal liver cell chimeric mice carrying the gene that encodes PrPC (Prnp) solely on hematopoietic or on stromal cells. We fractionated spleens at various times after intraperitoneal challenge with prions, and assayed infectivity by bioassay. Upon high-dose challenge, chimeras carrying PrPC on hematopoietic cells accumulated prions in stroma and in purified splenocytes. Instead, upon low-dose challenge ablation of Prnp in either compartment prevented splenic accumulation of infectivity, indicating that optimal prion replication requires PrPC expression by both stromal and hematopoietic compartments.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 98.0201