Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

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.

Demyelinating strain of mouse hepatitis virus infection bridging innate and adaptive immune response in the induction of demyelination

“…in addition, the MHV-induced model of CNS demyelinating disease used in the current studies shares many histopathologic features with the human disease MS, as well other viral-induced and autoimmune MS animal models [3,[39][40][41][42]. Features include inflammatory cell (Fig.…”

The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling of Physiological Fluids

“…More recently, precise cellular immunological and immunochemical studies of EAN models allowed researchers to partially uncover the mechanisms of GBS development and pathogenesis (8,9). Comparable methodologies have described the induction and immunological features of EAN as the GBS model of peripheral neurodegeneration and experimental allergic encephalomyelitis (EAE) as the model for multiple sclerosis (MS), which lead to neurodegeneration in the central nervous system and thereby provide additional opportunities for speculating about the etiology of these diseases (9,10).…”

Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms

“…Interestingly, intracranial inoculation of murine coronavirus (mouse hepatic virus (MHV)), induces optic neuritis and focal encephalitis leading to chronic demyelination in mice [83]. In this case, both innate and adaptive immune responses comprising of activation of microglia, B cells, CD4 T cells, and CD8 T cells along with the direct viral toxicity are proposed to mediate myelin stripping [68,70].…”