Intestinal immunity of Escherichia coli NISSLE 1917: a safe carrier for therapeutic molecules.
Intestinal immunity of Escherichia coli NISSLE 1917: a safe carrier for therapeutic molecules.
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DOI：
10.1016/j.femsim.2004.10.023
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发表时间：
2005-03
影响因子：
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通讯作者：
A. Westendorf;F. Gunzer;S. Deppenmeier;Damini Tapadar;J. Hunger;M. A. Schmidt;J. Buer;D. Bruder-
中科院分区：
文献类型：
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作者：
A. Westendorf;F. Gunzer;S. Deppenmeier;Damini Tapadar;J. Hunger;M. A. Schmidt;J. Buer;D. Bruder-
开发新的方法，使治疗药物准确靶向肠粘膜是肠道炎症研究的主要任务。荷兰当局首次批准活的转基因细菌菌株作为人类肠道疾病（IBD）实验治疗的治疗剂。转基因益生菌可以很好地用作载体，用于将局部抗原递送到肠道中。然而，这种载体生物体的治疗安全性是至关重要的，特别是当必须在疾病条件下使用特定益生菌菌株时。在这项研究中，我们测试的潜力ofEscherichia coliNISSLE 1917作为一个安全的载体，有针对性地传递重组蛋白到肠粘膜。在一个明确的和非常敏感的免疫系统中，我们证明了肠道重组E。coliNISSLE 1917对健康小鼠和急性结肠炎动物的特异性CD4+T细胞的迁移、克隆扩增和活化状态均无影响。此外，重组E. coliNISSLE 1917对自身免疫环境中外周T细胞耐受的诱导或破坏没有影响。E. coliNISSLE 1917使该菌株成为用于治疗分子的肠道聚焦原位合成的载体生物体的理想候选者。
The development of novel approaches that allow accurate targeting of therapeutics to the intestinal mucosa is a major task in the research on intestinal inflammation. For the first time, a live genetically modified bacterial strain has been approved by Dutch authorities as a therapeutic agent for experimental therapy of intestinal bowel disease (IBD) in humans. Genetically modified probiotics can very well be used as carriers for localized antigen delivery into the intestine. Therapeutic safety, however, of such a carrier organism, is crucial, especially when a specific probiotic strain has to be used under diseased conditions. In this study, we tested the potential ofEscherichia coliNISSLE 1917 to serve as a safe carrier for targeted delivery of recombinant proteins to the intestinal mucosa. In a well-defined and very sensitive immunological system, we demonstrate that intestinal recombinantE. coliNISSLE 1917 has no effect on migration, clonal expansion and activation status of specific CD4+T cells, neither in healthy mice nor in animals with acute colitis. Furthermore, recombinantE. coliNISSLE 1917 has no effect on the induction or breakdown of peripheral T-cell tolerance in an autoimmune environment. The excellent colonization properties ofE. coliNISSLE 1917 render this strain an ideal candidate as carrier organism for gut-focused in situ synthesis of therapeutic molecules.