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Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice
- Source :
- PLoS ONE, Vol 8, Iss 12, p e80128 (2013), PLoS ONE, PLoS ONE, Public Library of Science, 2013, 8 (12), pp.e80128. ⟨10.1371/journal.pone.0080128⟩, PLoS ONE, 2013, 8 (12), pp.e80128. ⟨10.1371/journal.pone.0080128⟩
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- International audience; 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.
- Subjects :
- Central Nervous System
Encephalomyelitis
Lipopolysaccharide Receptors
Gene Expression
Pregnancy Proteins
medicine.disease_cause
Autoimmunity
Mice
0302 clinical medicine
Cells, Cultured
Mice, Knockout
0303 health sciences
Multidisciplinary
Microglia
Recombinant Proteins
3. Good health
medicine.anatomical_structure
[SDV.IMM]Life Sciences [q-bio]/Immunology
Medicine
Research Article
Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
[SDV.IMM] Life Sciences [q-bio]/Immunology
Science
Biology
Proinflammatory cytokine
Myelin oligodendrocyte glycoprotein
03 medical and health sciences
Adjuvants, Immunologic
medicine
Animals
Humans
Neuroinflammation
030304 developmental biology
Innate immune system
Gene Products, env
Dendritic Cells
medicine.disease
Immunity, Innate
Peptide Fragments
Mice, Inbred C57BL
Toll-Like Receptor 4
Disease Models, Animal
Immunology
TLR4
biology.protein
Myelin-Oligodendrocyte Glycoprotein
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....5d245a52a9eefc44c657969a22d77023