title: Early IFN-γ production together with decreased expression of TLR3 and TLR9 characterizes EAE development conditional on the presence of myelin.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a model for the study of multiple sclerosis, which is an inflammatory and demyelinating disease of the central nervous system (CNS). Despite increased efforts to elucidate the function of toll-like receptors (TLRs) in autoimmune diseases of the CNS, the relative contribution of other factors, including the immunomodulatory properties of TLR signaling, role of the innate response and the presence or absence of myelin peptides remain unclear. The aim was to evaluate TLR expression in the CNS during EAE development by investigating the expression of TLRs in the initial phase of EAE and establishing correlations with the modulation of inflammatory factors. Mice were subcutaneously immunized at the tail base with 100 μg of myelin oligodendrocyte glycoprotein peptide (MOG35-55), emulsified in complete Freund's adjuvant (CFA) supplemented with 400 μg of attenuated Mycobacterium tuberculosis H37RA. Pertussis toxin (300 ng per animal) was intraperitoneally injected on the day of immunization and 48 h later. Another group (MOG(-)) received an equal emulsion of CFA and M. tuberculosis, without MOG35-55, and the same protocol of Pertussis toxin. The immunized mice presented signs of disease with increased IFN-γ production and presence of NK cells on Day 2 postimmunization and reduced the expression of TLR-3 and TLR-9. In the spinal cord, CCL5 and CCL20 were higher in EAE. This study establishes a correlation between TLR-3 and TLR-9 expression with the development of EAE. In addition, evidence of a role for the myelin peptide in targeting the innate inflammatory response to the CNS is presented.
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Marcilene Gomes
authors.initials: MG
authors.lastname: Evangelista
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .|b Department of Pharmacy , Federal University of Juiz de Fora , Governador Valadares , Brazil .
authors.forename: Sandra Bertelli Ribeiro De
authors.initials: SB
authors.lastname: Castro
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .|c Faculty of Medicine , Federal University of the Valleys of Jequitinhonha and Mucuri , Teófilo Otoni , Brazil .
authors.forename: Caio César De Souza
authors.initials: CC
authors.lastname: Alves
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Alyria Teixeira
authors.initials: AT
authors.lastname: Dias
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Viano Wyallison De
authors.initials: VW
authors.lastname: Souza
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Lívia Bittencourt Dos
authors.initials: LB
authors.lastname: Reis
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Luan Cristian Da
authors.initials: LC
authors.lastname: Silva
authors.affiliation: d Department of Morphology , Federal University of Juiz de Fora , Juiz de Fora , Brazil , and.
authors.forename: Maria Christina Marques Nogueira
authors.initials: MC
authors.lastname: Castañon
authors.affiliation: d Department of Morphology , Federal University of Juiz de Fora , Juiz de Fora , Brazil , and.
authors.forename: Rogério Estevam
authors.initials: RE
authors.lastname: Farias
authors.affiliation: e Department of Biophysics , Federal University of São Paulo , São Paulo , Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Juliano
authors.affiliation: a IMUNOCET - Department of Parasitology, Microbiology and Immunology , Institute of Biological Sciences, Federal University of Juiz de Fora , Juiz de Fora , Brazil .
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma
keywords: EAE; IFN-γ; Multiple sclerosis; toll-like