Processing of the Bovine Spongiform Encephalopathy-Specific Prion Protein by Dendritic Cells

Abstract

Dendritic cells (DC) are suspected to be involved in transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE). We detected the disease-specific, protease-resistant prion protein (PrP bse ) in splenic DC purified by magnetic cell sorting 45 days after intraperitoneal inoculation of BSE prions in immunocompetent mice. We showed that bone marrow-derived DC (BMDC) from wild-type or PrP-null mice acquired both PrP bse and prion infectivity within 2 h of in vitro culture with a BSE inoculum. BMDC cleared PrP bse within 2 to 3 days of culture, while BMDC infectivity was only 10-fold diminished between days 1 and 6 of culture, suggesting that the infectious unit in BMDC is not removed at the same rate as PrP bse is removed from these cells. Bone marrow-derived plasmacytoid DC and bone marrow-derived macrophages (BMM) also acquired and degraded PrP bse when incubated with a BSE inoculum, with kinetics very similar to those of BMDC. PrP bse capture is probably specific to antigen-presenting cells since no uptake of PrP bse was observed when splenic B or T lymphocytes were incubated with a BSE inoculum in vitro. Lipopolysaccharide activation of BMDC or BMM prior to BSE infection resulted in an accelerated breakdown of PrP bse . Injected by the intraperitoneal route, BMDC were not infectious for alymphoid recombination-activated gene 2 0 /common cytokine ␥ chain-deficient mice, suggesting that these cells are not capable of directly propagating BSE infectivity to nerve endings.

A Specific Population of Abnormal Prion Protein Aggregates Is Preferentially Taken Up by Cells and Disaggregated in a Strain-Dependent Manner

“…2 and 5 (14,(30)(31)(32)(33)(34), and PrP Sc in scrapie-infected cells can be degraded by cocultivation with dendritic cells (35,36). Our data demonstrate that cells disaggregate PrP Sc within the first 24 h following infection with scrapie.…”

Prion Protein Expression by Mouse Dendritic Cells Is Restricted to the Nonplasmacytoid Subsets and Correlates with the Maturation State

“…Indeed, DCs were shown to transport prions to the mesenteric lymph after oral inoculation (26), and to transfer prion infection to the brain (27). Other studies suggest that DCs can degrade TSE agents (28,29), as do macrophages (30).…”

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

“…The role of DCs in prion disease appears to be ambiguous. Some authors have shown, through in vitro models, that DCs can impair prion dissemination and that they are able to process PrP Sc , by cysteine protease, and to decrease the amount of infectivity associated with scrapie (Luhr et al 2002(Luhr et al , 2004 or BSE (Rybner-Barnier et al 2006). Several studies have demonstrated that DCs act in the spreading of prions.…”