Antibiotics protect against EAE by increasing regulatory and anti-inflammatory cells
Antibiotics protect against EAE by increasing regulatory and anti-inflammatory cells
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DOI：
10.1007/s11011-018-0266-7
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发表时间：
2018-10-01
影响因子：
3.6
通讯作者：
Offner, Halina
中科院分区：
文献类型：
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作者：
Seifert, Hilary A.;Benedek, Gil;Offner, Halina
口服抗生素鸡尾酒（氨苄青霉素、甲硝唑、硫酸新霉素和万古霉素）的7天预处理过程显示诱导外周免疫调节的变化，并保护小鼠免受实验性自身免疫性脑脊髓炎（EAE）的体征。为了确定较短疗程的抗生素预处理是否也可以保护小鼠免受EAE并诱导调节性免疫细胞，使用相同的口服抗生素鸡尾酒进行了三天的研究。此外，还检查了CNS以确定抗生素预处理对EAE病程和受影响组织内免疫调节的影响。较短的三天预处理疗程也显著保护C57 BL/6小鼠免受严重EAE。此外，我们的研究发现，在EAE保护小鼠的脾脏中，调节细胞的频率增加，抗炎巨噬细胞的频率减少。此外，在来自脊髓的mRNA上运行的趋化因子和趋化因子受体阵列显示，与调节性T细胞和巨噬细胞募集相关的基因在抗生素预处理的小鼠中强烈上调。另外的RT-PCR数据显示与抗炎小胶质细胞/巨噬细胞相关的基因上调，促炎基因下调。这表明由趋化因子募集到脊髓的巨噬细胞随后被极化为抗炎表型。这些结果有力地支持了这样的结论：在诱导严重EAE之前给予为期三天的抗生素治疗，通过诱导外周调节性淋巴细胞和受影响脊髓组织中的抗炎环境，极大地保护了小鼠。
A seven day pretreatment course of an oral antibiotic cocktail (Ampicillin, Metronidazole, Neomycin Sulfate, and Vancomycin) was shown to induce changes in peripheral immune regulation and protect mice from signs of experimental autoimmune encephalomyelitis (EAE). To determine if a shorter course of antibiotic pretreatment could also protect the mice from EAE and induce regulatory immune cells, studies were conducted using the same oral antibiotic cocktail for three days. In addition, the CNS was examined to determine the effects of antibiotic pretreatment on EAE disease course and immune modulation within the affected tissue. The shorter three day pretreatment course was also significantly protective against severe EAE in C57BL/6 mice. Moreover, our study found increased frequencies of regulatory cells and a decrease in the frequency of anti-inflammatory macrophages in the spleen of EAE protected mice. Additionally, a chemokine and chemokine receptor array run on mRNA from spinal cords revealed that genes associated with regulatory T cells and macrophage recruitment were strongly upregulated in the antibiotic pretreated mice. Additional RT-PCR data showed genes associated with anti-inflammatory microglia/macrophages were upregulated and pro-inflammatory genes were downregulated. This suggests the macrophages recruited to the spinal cord by chemokines are subsequently polarized toward an anti-inflammatory phenotype. These results lend strong support to the conclusion that a three day course of antibiotic treatment given prior to the induction of severe EAE profoundly protected the mice by inducing regulatory lymphocytes in the periphery and an anti-inflammatory milieu in the affected spinal cord tissue.