Different mechanisms of inflammation induced in virus and autoimmune-mediated models of multiple sclerosis in C57BL6
Abhinoy Kishore1, Anurag Kanaujia, Soma Nag
1Department of Biological Sciences, Indian Institute of Science Education and Research-Kolkata, Mohanpur, Nadia West Bengal 741252, India.
Abstract:
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.
Insights
Comparing viral and autoimmune models of multiple sclerosis (MS) in mice reveals distinct inflammatory patterns. These differences in central nervous system (CNS) pathology may explain why immunosuppression often fails in treating MS.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Pathology
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS.
- Viral (MHV-A59) and autoimmune (MOG-induced EAE) models exhibit MS-like pathology.
- Mechanisms include microglia-mediated myelin stripping, axonal injury, and T-cell involvement.
Purpose of the Study:
- Directly compare CNS pathology in viral-induced and autoimmune MS models.
- Investigate similarities and differences in demyelination and inflammation.
- Elucidate potential reasons for treatment resistance in MS.
Main Methods:
- Induction of demyelinating disease in mice using MHV-A59 (viral) and MOG immunization (autoimmune EAE).
- Comparative analysis of central nervous system (CNS) pathology, including demyelination patterns, distribution, and inflammation over disease progression.
- Assessment of inflammatory cell infiltration in gray and white matter.
Main Results:
- Both viral-induced and EAE models showed similar demyelination patterns and distributions over time.
- Significant differences observed in acute inflammation: EAE primarily affected white matter, while MHV-induced disease initially impacted gray matter before localizing to white matter.
- Microglia-mediated myelin stripping and direct axonal injury were noted in the viral model.
Conclusions:
- Dual mechanisms of demyelination, encompassing both autoimmune and non-immune (viral toxicity) pathways, may contribute to MS pathogenesis.
- Distinct inflammatory patterns in viral versus autoimmune models highlight the complexity of MS.
- These findings suggest that the heterogeneity of MS pathology could underlie the limited efficacy of immunosuppressive therapies in achieving long-term remission.
