title: Prion pathogenesis is unaltered following down-regulation of SIGN-R1.
abstract: Prion diseases are infectious neurodegenerative disorders characterised by accumulations of abnormal prion glycoprotein in affected tissues. Following peripheral exposure, many prion strains replicate upon follicular dendritic cells (FDC) in lymphoid tissues before infecting the brain. An intact splenic marginal zone is important for the efficient delivery of prions to FDC. The marginal zone contains a ring of specific intercellular adhesion molecule-3-grabbing non-integrin related 1 (SIGN-R1)-expressing macrophages. This lectin binds dextran and capsular pneumococcal polysaccharides, and also enhances the clearance of apoptotic cells via interactions with complement components. Since prions are acquired as complement-opsonized complexes we determined the role of SIGN-R1 in disease pathogenesis. We show that transient down-regulation of SIGN-R1 prior to intravenous prion exposure had no effect on the early accumulation of prions upon splenic FDC or their subsequent spread to the brain. Thus, SIGN-R1 expression by marginal zone macrophages is not rate-limiting for peripheral prion disease pathogenesis.
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Barry M
authors: BM
authors: Bradford
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Karen L
authors: KL
authors: Brown
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. Electronic address: neil.mabbott@roslin.ed.ac.uk.
authors: Neil A
authors: NA
authors: Mabbott
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015536:Down-Regulation; D005786:Gene Expression Regulation; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D017096:Prion Diseases / Q000209:etiology* / Q000378:metabolism*; D000072002:Prion Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D000072002:Prion Proteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: Follicular dendritic cell; Macrophage; Marginal zone; Prions; Specific intercellular adhesion molecule-3-grabbing non-integrin related 1 (SIGN-R1); Spleen; Transmissible spongiform encephalopathies