title: The clinical course of experimental autoimmune encephalomyelitis is associated with a profound and sustained transcriptional activation of the genes encoding toll-like receptor 2 and CD14 in the mouse CNS.
abstract: Experimental autoimmune encephalomyelitis (EAE) is an autoimmune demyelinating disease commonly used to model the pathogenetic mechanisms involved in multiple sclerosis (MS). In this study, we examined the effects of immunization with the myelin oligodendrocyte glycoprotein MOG(35-55) on the expression of molecules of the innate immune system, namely toll-like receptor 2 (TLR2) and CD14. Expression of the mRNA encoding TLR2 increased in the choroid plexus, the leptomeninges and within few isolated cells in the CNS parenchyma 4 to 8 days after immunization with MOG. At day 10, the signal spread across the meninges, few perivascular regions and over isolated groups of parenchymal cells. Three weeks after the MOG treatment, at which time animals showed severe clinical symptoms, a robust expression of both TLR2 and CD14 transcripts occurred in barrier-associated structures, as well as parenchymal elements of the spinal cord, and within numerous regions of the brain including, the medulla, cerebellum and the cortex. Dual labeling provided the anatomical evidence that microglia/macrophages were positive for TLR2 in the brain of EAE mice. The regions that exhibited chronic expression of TLR2 and CD14 were also associated with an increase in NF-kappaB activity and transcriptional activation of genes encoding numerous proinflammatory molecules. The present data provide evidence that receptors of the pathogen-associated molecular patterns are strongly induced in the CNS of EAE mice, further reinforcing the concept that the innate immune system plays a determinant role in this autoimmune demyelinating disease.
authors.affiliation: CHUL Research Center and Department of Anatomy and Physiology, Laval University, Laurier, Québec, Canada. serge.rivest@crchul.ulaval.ca
authors.forename: Hakima
authors.initials: H
authors.lastname: Zekki
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Feinstein
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006023:Glycoproteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015533:Transcriptional Activation / Q000276:immunology; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C445081:myelin oligodendrocyte glycoprotein (35-55)