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

Abstract

Expression of the physiological cellular prion protein (PrPC) is remarkably regulated during differentiation and activation of cells of the immune system. Among these, dendritic cells (DCs) display particularly high levels of membrane PrPC, which increase upon maturation, in parallel with that of molecules involved in Ag presentation to T cells. Freshly isolated mouse Langerhans cells, dermal DCs, and DCs from thymus, spleen, and mesenteric lymph nodes expressed low to intermediate levels of PrPC. Highest levels of both PrPC and MHC class II molecules were displayed by lymph node CD8αint DCs, which represent fully mature cells having migrated from peripheral tissues. Maturation induced by overnight culture resulted in increased levels of surface PrPC, as did in vivo DC activation by bacterial LPS. Studies on Fms-like tyrosine kinase 3 ligand bone marrow-differentiated B220− DCs confirmed that PrPC expression followed that of MHC class II and costimulatory molecules, and correlated with IL-12 production in response to TLR-9 engagement by CpG. However, at variance with conventional DCs, B220+ plasmacytoid DCs isolated from the spleen, or in vitro differentiated, did not significantly express PrPC, both before and after activation by TLR-9 engagement. PrP knockout mice displayed higher numbers of spleen CD8α+ DCs, but no significant differences in their maturation response to stimulation through TLR-4 and TLR-9 were noticed. Results are discussed in relation to the functional relevance of PrPC expression by DCs in the induction of T cell responses, and to the pathophysiology of prion diseases.

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

“…4). It suggests that speciWcally maturing DCs express PrP C , as demonstrated in vivo (Martinez del et al 2006;Dorban et al 2007b). Freshly isolated peripheral neurons cultured for 48 h expressed PrP C within the perikaryon and neurites (Fig.…”

Physiological role of the cellular prion protein

“…PrP C was found on the surface of bone marrowderived human and mouse DC generated in vitro in the presence of GMCSF, at levels that increased with LPS stimulation and correlated with that of MHC II and costimulatory molecule CD86 [3,15]. Higher PrP C levels were found on the surface of spleen DC that are also CD8α+; expression of this marker has been correlated with the secretion of IL-12 and IFN-α [61]. In lymph nodes, the highest PrP C level was observed in the CD8int subset, which are strong stimulators of Ag-dependent delayed-type hypersensitivity.…”

“…In lymph nodes, the highest PrP C level was observed in the CD8int subset, which are strong stimulators of Ag-dependent delayed-type hypersensitivity. This was interpreted as a possible involvement of PrP C in T cell activation leading to Th1 responses [61]. However, the mechanisms involved in T cell activation related to PrP C expressed on DC remain to be explored.…”

Selection of an Antibody Library Identifies a Pathway to Induce Immunity by Targeting CD36 on Steady-State CD8α+ Dendritic Cells

“…Bone marrow-derived DCs (BMDCs) were generated using Fms-like tyrosine kinase 3 ligand as described previously (18). DCs were used at day 10 and purity of CD11c ϩ was higher than 90%.…”

“…OT-II and OT-I cells were isolated from total lymph node (LN) suspensions by negative selection using a MACS isolation kit (Miltenyi Biotec). Langerhans cells and dermal DCs were isolated from the epidermis as described previously (18).…”