title: Transcriptional modulation in a leukocyte-depleted splenic cell population during prion disease.
abstract: Prion replication in the periphery precedes neuroinvasion in many experimental rodent scrapie models, and in natural sheep scrapie and chronic wasting disease (CWD) in cervids. Prions propagate in the germinal centers of secondary lymphoid organs and are strongly associated with follicular dendritic cells (FDC) and possibly circulating dendritic cells and macrophages. Given the importance of lymphoid organs in prion disease transmission and pathogenesis, gene expression studies may reveal host factors or biological pathways related to prion replication and accumulation. A procedure was developed to enrich for FDC, dendritic cells, and macrophages prior to the investigation of transcriptional alterations in murine splenic cells during prion pathogenesis. In total, 1753 transcripts exhibited fold changes greater than three (false discovery rates less than 2%) in this population isolated from spleens of prion-infected versus uninfected mice. The gene for the small leucine-rich proteoglycan decorin (DCN) was one of the genes most overexpressed in infected mice, and the splenic protein levels mirrored this in mice infected with scrapie as well as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD). A number of groups of functionally related genes were also significantly decreased in infected spleens. These included genes related to iron metabolism and homeostasis, pathways that have also been implicated in prion pathogenesis in the brain. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as a pool of potential surrogate markers for the early detection and diagnosis of some prion diseases.
authors: Molecular PathoBiology, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors: Rhiannon L C H
authors: RL
authors: Huzarewich
authors: Sarah
authors: S
authors: Medina
authors: Catherine
authors: C
authors: Robertson
authors: Debra
authors: D
authors: Parchaliuk
authors: Stephanie A
authors: SA
authors: Booth
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D058575:Decorin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D017096:Prion Diseases / Q000175:diagnosis* / Q000276:immunology / Q000635:transmission / Q000662:veterinary; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D058575:Decorin; D011328:Prions