PloS one, 2013-12, Vol.8 (12), p.e80128
2013
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- Autor(en) / Beteiligte
- Titel
- Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice
- Ist Teil von
- PloS one, 2013-12, Vol.8 (12), p.e80128
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0080128Titel-ID: cdi_plos_journals_1465554248
- Format
- –
- Schlagworte
- Adjuvants, Immunologic - administration & dosage, Amino acids, Animal models, Animals, Autoimmunity, Brain, Brain damage, Cell activation, Cells, Cultured, Central Nervous System, Chemical compounds, Dendritic Cells, Disease, Disease Models, Animal, Encephalomyelitis, Encephalomyelitis, Autoimmune, Experimental - chemically induced, Encephalomyelitis, Autoimmune, Experimental - genetics, Encephalomyelitis, Autoimmune, Experimental - immunology, Encephalomyelitis, Autoimmune, Experimental - pathology, Envelope protein, Experimental allergic encephalomyelitis, Freund's adjuvant, Gene Expression, Gene Products, env - administration & dosage, Gene Products, env - immunology, Genomes, Herpes viruses, Human behavior, Humans, Immunity, Immunity, Innate - drug effects, Immunology, Inducers, Inflammation, Innate immunity, Lesions, Life Sciences, Lipopolysaccharide Receptors - genetics, Lipopolysaccharide Receptors - immunology, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, Multiple sclerosis, Multiple Sclerosis - genetics, Multiple Sclerosis - immunology, Multiple Sclerosis - pathology, Myelin, Myelin proteins, Myelin-Oligodendrocyte Glycoprotein - administration & dosage, Nervous system, Oligodendrocyte-myelin glycoprotein, Peptide Fragments - administration & dosage, Pharmacology, Pregnancy Proteins - administration & dosage, Pregnancy Proteins - immunology, Proteins, Recombinant Proteins - administration & dosage, Recombinant Proteins - immunology, Rodents, Studies, TLR4 protein, Toll-Like Receptor 4 - deficiency, Toll-Like Receptor 4 - genetics, Toll-Like Receptor 4 - immunology, Toll-like receptors, Viral envelope proteins