scholarly journals The Interdependent, Overlapping, and Differential Roles of Type I and II IFNs in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 191 (6) ◽  
pp. 2967-2977 ◽  
Author(s):  
Rodrigo Naves ◽  
Simer P. Singh ◽  
Kevin S. Cashman ◽  
Amber L. Rowse ◽  
Robert C. Axtell ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2019 ◽  
Author(s):  
Abdollah Jafarzadeh ◽  
Maryam Nemati ◽  
Hossain Khorramdelazad ◽  
Abbas Mirshafiey
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Wide Spectrum ◽  
Γδ T Cells ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Amyloid A ◽  
Molecular Patterns ◽  
Experimental Autoimmune

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys­tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of  DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review. 

scholarly journals Central Nervous System-Endogenous TLR7 and TLR9 Induce Different Immune Responses and Effects on Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Ruthe Storgaard Dieu ◽  
Vian Wais ◽  
Michael Zaucha Sørensen ◽  
Joanna Marczynska ◽  
Magdalena Dubik ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Onset ◽  
Protective Role ◽  
Type I ◽  
Type I Ifn ◽  
Autoimmune Encephalomyelitis ◽  
Tlr9 Signaling ◽  
Experimental Autoimmune

Innate receptors, including Toll like receptors (TLRs), are implicated in pathogenesis of CNS inflammatory diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). TLR response to pathogens or endogenous signals includes production of immunoregulatory mediators. One of these, interferon (IFN)β, a Type I IFN, plays a protective role in MS and EAE. We have previously shown that intrathecal administration of selected TLR ligands induced IFNβ and infiltration of blood-derived myeloid cells into the central nervous system (CNS), and suppressed EAE in mice. We have now extended these studies to evaluate a potential therapeutic role for CNS-endogenous TLR7 and TLR9. Intrathecal application of Imiquimod (TLR7 ligand) or CpG oligonucleotide (TLR9 ligand) into CNS of otherwise unmanipulated mice induced IFNβ expression, with greater magnitude in response to CpG. CD45+ cells in the meninges were identified as source of IFNβ. Intrathecal CpG induced infiltration of monocytes, neutrophils, CD4+ T cells and NK cells whereas Imiquimod did not recruit blood-derived CD45+ cells. CpG, but not Imiquimod, had a beneficial effect on EAE, when given at time of disease onset. This therapeutic effect of CpG on EAE was not seen in mice lacking the Type I IFN receptor. In mice with EAE treated with CpG, the proportion of monocytes was significantly increased in the CNS. Infiltrating cells were predominantly localized to spinal cord meninges and demyelination was significantly reduced compared to non-treated mice with EAE. Our findings show that TLR7 and TLR9 signaling induce distinct inflammatory responses in the CNS with different outcome in EAE and point to recruitment of blood-derived cells and IFNβ induction as possible mechanistic links between TLR9 stimulation and amelioration of EAE. The protective role of TLR9 signaling in the CNS may have application in treatment of diseases such as MS.

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