Selective expression of prion protein in peripheral tissues of the adult mouse.
The level of expression of normal cellular prion protein, PrP(c) (cellular prion protein), controls both the rate and the route of neuroinvasive infection, from peripheral entry portal to the CNS. Paradoxically, an overview of the distribution of PrP(c) within tissues outside the CNS is lacking. We have used novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue (in order to optimise immunohistochemical labelling of this conformationally labile protein), in combination with in situ hybridisation, to examine the expression of PrP(c) in peripheral tissues of the adult mouse. We found that although prion protein is expressed in many tissues, it is expressed at high levels only in discrete subpopulations of cells. Prominent amongst these are elements of the "hardwired neuroimmune network" that integrate the body's immune defence and neuroendocrine systems under CNS control. These prion protein-expressing elements include small diameter afferent nerves in the skin and the lamina propria of the aerodigestive tract, sympathetic ganglia and nerves, antigen presenting and processing cells (both follicular and non-follicular dendritic cells) and sub-populations of lymphocytes particularly in skin, gut- and bronchus-associated lymphoid tissues. Prion protein is also expressed in the parasympathetic and enteric nervous systems, in the dispersed neuroendocrine system, and in peripheral nervous system axons and their associated Schwann cells. This selective expression of cellular prion protein provides a variety of alternative routes for the propagation and transport of prion infection entering from peripheral sites, either naturally (via the aerodigestive tract or abraded skin) or experimentally (by intraperitoneal injection) to the brain. Key regulatory cells that express prion protein, and in particular enteroendocrine cells in the mucosal wall of the gut, and dendritic cells that convey pathogens from epithelial layers to secondary lymphoid organs, may be particularly important in the transmission of infection in the periphery.
Ford
M J
MJ
MRC Centre for Developmental Neurobiology, Hodgkin Building, King's College London Guy's Campus, London Bridge, London SE1 1UL, UK
Burton
L J
LJ
Morris
R J
RJ
Hall
S M
SM
D000818:Animals; D015153:Blotting, Western; D004064:Digestive System / Q000737:chemistry; D007107:Immune System / Q000737:chemistry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009420:Nervous System / Q000737:chemistry; D018621:PrPC Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012137:Respiratory System / Q000737:chemistry; D014018:Tissue Distribution; D014566:Urogenital System / Q000737:chemistry
D018621:PrPC Proteins; D012333:RNA, Messenger