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首页> 外文期刊>Journal of neuroinflammation >IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease
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IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

机译：IL-1信号影响病毒诱导的慢性中枢神经系统脱髓鞘疾病的保护和发病机制

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Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS). IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE) and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO) were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU). Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6) mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of inhibitory cytokines and regulatory molecules. Therefore, the balance of IL-1 signaling appears to be extremely important for the protection from TMEV-induced demyelinating disease, and either too much or too little signaling promotes the development of disease.
机译：背景技术Theiler的病毒感染可在小鼠中诱发慢性脱髓鞘疾病，并已作为多发性硬化症（MS）的感染模型进行了研究。 IL-1在自身免疫疾病模型（EAE）和该MS病毒模型的发病机理中均起着重要作用。但是，已知IL-1对某些病毒感染起着重要的保护作用。因此，尚不清楚IL-1介导的信号传导在TMEV诱导的脱髓鞘疾病的发展中起保护作用还是致病作用。方法用Theiler鼠脑脊髓炎病毒（1 x 106 PFU）感染雌性C57BL / 6小鼠和B6.129S7-Il1r1tm1Imx / J小鼠（IL-1R KO）。比较了脱髓鞘疾病的发展和组织病理学变化的差异。使用定量PCR，ELISA和流式细胞仪分析了感染小鼠中枢神经系统中的病毒持久性，细胞因子产生和免疫反应。结果施用IL-1β，从而使易受TMEV诱导的脱髓鞘疾病的抗性B6小鼠诱导高水平的Th17应答。有趣的是，将TMEV感染到IL-1R缺乏的抗性C57BL / 6（B6）小鼠中也引起了TMEV诱导的脱髓鞘疾病。在IL-1R缺陷型小鼠的病毒感染后期发现了高病毒持久性，尽管在WT B6和IL-1R缺陷型小鼠之间最初的抗病毒免疫反应和病毒持久性水平差异不大。最初的I型IFN应答以及PDL-1和Tim-3的表达在TMEV感染的IL-1R缺陷型小鼠的中枢神经系统中更高，导致T细胞功能缺陷，从而导致病毒的持久性。结论这些结果表明，高IL-1水平的存在通过升高致病性Th17反应发挥了致病作用，而缺乏IL-1信号则由于T细胞活化不足而导致脊髓中的病毒持续性增强，这是通过增加抑制性产生细胞因子和调节分子。因此，IL-1信号的平衡对于保护免受TMEV诱导的脱髓鞘疾病极为重要，并且信号过多或过少都会促进疾病的发展。

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