多発性硬化症の発症および進行と細菌因子を結びつける潜在的なメカニズム

Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease of the central nervous system (CNS). While the exact etiology remains unclear, emerging evidence suggests that bacterial toxins play significant roles in MS pathogenesis and progression. We aimed to review mechanisms by which bacterial toxins influence MS development, focusing on molecular mimicry, epitope spreading, bystander activation, and blood-brain barrier (BBB) disruption. Specific toxins, including Clostridium perfringens epsilon toxin, Staphylococcus aureus superantigens, and Chlamydia pneumoniae heat shock proteins, demonstrate distinct pathogenic mechanisms in promoting CNS inflammation. Crucially, several toxins disrupt BBB integrity, making it easier for immune cells and cytokines that promote inflammation to enter the CNS and exacerbate neural inflammation. Furthermore, through molecular mimicry and epitope dissemination, bacterial antigens can initiate cross-reacting immune responses that may lead to autoimmune attacks on myelin. This review highlights the complex interplay between bacterial toxins, immune modulation, and genetic susceptibility in MS. Understanding these toxin-mediated pathways reveals the complex interplay between the microbiome and MS pathogenesis, potentially leading to novel therapeutic interventions targeting bacterial contributions to autoimmune neurodegeneration.