Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways
Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways
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DOI：
10.1128/iai.01449-05
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发表时间：
2006-07-01
影响因子：
3.1
通讯作者：
Sturm, A.
中科院分区：
文献类型：
--
作者：
Grabig, A.;Paclik, D.;Sturm, A.
Toll样受体（TLR）是先天免疫系统的关键组分，其触发抗微生物宿主防御反应。本研究的目的是分析益生菌大肠杆菌Nissle菌株1917对TLR-2和TLR-4基因敲除小鼠诱导的实验性结肠炎的影响。通过施用5%葡聚糖硫酸钠（DSS）在野生型（wt）、TLR-2敲除和TLR-4敲除小鼠中诱导结肠炎。用0.9%NaCl或107 E处理小鼠。coli Nissle 1917每天两次，随后测定疾病活动性、粘膜损伤和细胞因子分泌。暴露于DSS的野生型和TLR-2敲除小鼠发生急性结肠炎，而TLR-4敲除小鼠发生显著较少的炎症。在野生型小鼠中，而不是TLR-2或TLR-4敲除小鼠中，E. coli Nissle 1917改善结肠炎并减少促炎细胞因子分泌。在TLR-2基因敲除小鼠中，在E. coli Nissle 1917处理。在TLR-4基因敲除小鼠中，细胞因子分泌几乎检测不到，并且不受E. coli Nissle 1917，表明TLR-4敲除小鼠不发生与野生型小鼠相似的结肠炎。共培养E. coli Nissle 1917和人T细胞通过TLR-2和TLR-4增加T细胞中TLR-2和TLR-4蛋白的表达并增加NF-κ B B活性。总之，我们的数据提供了证据，E。coli Nissle 1917通过TLR-2和TLR-4依赖性途径改善小鼠实验诱导的结肠炎。
Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 107 E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-kappa B activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.