title: Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure.
abstract: The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node.
authors.affiliation: Institute for Animal Health, Edinburgh, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mohan
authors.forename: John
authors.initials: J
authors.lastname: Hopkins
authors.forename: Neil A
authors.initials: NA
authors.lastname: Mabbott
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000382:microbiology; D002454:Cell Differentiation; D002460:Cell Line; D015870:Gene Expression; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D018621:PrPC Proteins / Q000096:biosynthesis / Q000235:genetics; D018620:PrPSc Proteins / Q000096:biosynthesis / Q000235:genetics / Q000472:pathogenicity*; D017096:Prion Diseases / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000382:microbiology*
chemical_list: D000954:Antigens, Surface; D008070:Lipopolysaccharides; D018621:PrPC Proteins; D018620:PrPSc Proteins; D012333:RNA, Messenger