Prion protein expression by mouse dendritic cells is restricted to the nonplasmacytoid subsets and correlates with the maturation state.
Expression of the physiological cellular prion protein (PrP(C)) is remarkably regulated during differentiation and activation of cells of the immune system. Among these, dendritic cells (DCs) display particularly high levels of membrane PrP(C), 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 PrP(C). Highest levels of both PrP(C) and MHC class II molecules were displayed by lymph node CD8alpha(int) DCs, which represent fully mature cells having migrated from peripheral tissues. Maturation induced by overnight culture resulted in increased levels of surface PrP(C), as did in vivo DC activation by bacterial LPS. Studies on Fms-like tyrosine kinase 3 ligand bone marrow-differentiated B220(-) DCs confirmed that PrP(C) 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 PrP(C), both before and after activation by TLR-9 engagement. PrP knockout mice displayed higher numbers of spleen CD8alpha(+) 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 PrP(C) expression by DCs in the induction of T cell responses, and to the pathophysiology of prion diseases.
Martínez del Hoyo
Gloria
G
Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Universidad Autónoma, Madrid, Spain.
López-Bravo
María
M
Metharom
Patraporn
P
Ardavín
Carlos
C
Aucouturier
Pierre
P
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D018621:PrPC Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D000949:Histocompatibility Antigens Class II; D018621:PrPC Proteins; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D051941:fms-Like Tyrosine Kinase 3; D017493:Leukocyte Common Antigens