Department of Medical Microbiology and Immunology, University of Turku, Turku University Hospital, Diagnostic and Related Services, Hospital District of Southwest Finland, Turku, Finland.
Acta Neurol Scand. 2017 Nov;136 Suppl 201:10-14. doi: 10.1111/ane.12838.
Multiple sclerosis is a multifaceted inflammatory-autoimmune disease, which shows remarkable heterogeneity in its clinical presentation, disease progression and in tissue lesions in the CNS. Focal lesions in white matter consist of immune effector cells, antibodies, and complement deposits in varying combinations, suggesting that immune mechanisms related to CNS pathology are multiple. Although adaptive immunity to myelin antigens is essential in MS pathogenesis, innate immune mechanisms are likely involved in its initiation and perpetuation. One key question is if recognition of infectious agents and microbial products by innate immune mechanisms impacts on MS and if so, how and where? This short review aims at conceptualizing how interactions between microbes and innate immune mechanisms could contribute to MS pathogenesis. Consideration is given to initiation of local inflammation and to myelin-specific immune responses, and how innate immunity and microbes may contribute to these. Recent advances in our understanding of lymphatic drainage of CNS, its immune surveillance and effects of gut microbiota and obesity on systemic endotoxin levels and T-cell priming may open new perspectives to understanding the roles that infectious agents and microbes may have in MS.
多发性硬化症是一种多方面的炎症性自身免疫性疾病，其临床表现、疾病进展和中枢神经系统组织损伤具有显著的异质性。白质中的局灶性病变包含免疫效应细胞、抗体和补体沉积物，其组合各不相同，这表明与中枢神经系统病理相关的免疫机制是多种多样的。虽然针对髓鞘抗原的适应性免疫在多发性硬化症的发病机制中至关重要，但先天免疫机制可能参与了其启动和持续。一个关键问题是，先天免疫机制对感染因子和微生物产物的识别是否会影响多发性硬化症，如果是，其影响方式和部位是什么？本文综述旨在阐明微生物与先天免疫机制之间的相互作用如何有助于多发性硬化症的发病机制。文中考虑了局部炎症的启动以及髓鞘特异性免疫反应，以及先天免疫和微生物如何促成这些反应。我们对中枢神经系统淋巴引流、免疫监视以及肠道微生物群和肥胖对全身内毒素水平和 T 细胞启动的影响的理解的最新进展，可能为理解感染因子和微生物在多发性硬化症中的作用开辟新的视角。
