Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.
Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.
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DOI：
10.1038/srep44377
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发表时间：
2017-03-14
影响因子：
4.6
通讯作者：
Guaza C
中科院分区：
文献类型：
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作者：
Carrillo-Salinas FJ;Mestre L;Mecha M;Feliú A;Del Campo R;Villarrubia N;Espejo C;Montalbán X;Álvarez-Cermeño JC;Villar LM;Guaza C
最近的研究已经开始指出微生物群对多发性硬化症（MS）发病机制的贡献。Theiler小鼠脑脊髓炎病毒诱导的脱髓鞘疾病（TMEV-IDD）是一种进行性MS模型。在这里，我们首先分析了TMEV脑内感染对脑内微生物群的影响，其次，早期微生物群耗竭是否影响急性期（14 dpi）对TMEV的免疫应答及其对慢性期（85 dpi）的影响。颅内接种TMEV与中度生态失调相关。口服广谱抗生素（ABX）可改变对TMEV的神经免疫应答，抑制急性期脑内CD 4+和CD 8 + T细胞浸润。细胞因子，趋化因子和VP 2衣壳蛋白的表达增强，并伴随着活化的小胶质细胞簇散布在整个大脑。此外，ABX处理的小鼠在颈部和肠系膜淋巴结中显示出较低水平的CD 4+和CD 8 +T细胞。在感染后第28天停止ABX后，观察到TMEV的死亡率增加。在慢性期，ABX停药后存活并恢复微生物群多样性的小鼠在脑细胞浸润、小胶质细胞和细胞因子基因表达方面表现出微妙的变化。因此，ABX-TMEV组的存活小鼠显示出与TMEV小鼠相似的疾病严重程度。
Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.