肠道免疫的安全靶向载体:大肠杆菌Nissle1917

Escherichia coli Nissle 1917 as safe vehicles for intestinal immune targeted therapy—A review

摘要:

摘要:长期以来，如何激发高效的肠道黏膜免疫应答来预防肠道感染始终是较为棘手的问题。本文旨在对大肠杆菌(Escherichia coli)Nissle 1917 作为肠道黏膜免疫的安全靶向载体，调理胃肠道菌群紊乱、缓解溃疡性结肠炎以及利用益生菌固有特性或优化特性进行治疗的可能性等相关研究进展作一综述。大肠杆菌Nissle1917(EcN)是一株可口服的优良益生菌，也可作为生物载体活苗候选株，兼有较强的肠道局部定殖能力和无免疫原性的特性。该菌株还可以作为载体靶向递呈TAT—凋亡素融合蛋白治疗结肠直肠癌，并在研发靶向递呈防御素治疗溃疡性结肠炎和克罗恩病上具有重要的功能。其基因修饰株能够原位递呈特定的抗原分子，有效激发特异性的黏膜免疫应答。重组大肠杆菌Nissle-HA110-120具有体外表达特异性抗原的能力，但EcN菌体本身不会引起黏膜免疫应答，也不影响对自身抗原的外周免疫耐受。同时，EcN具有很好的安全性，尤其是因炎症导致肠道防御屏障破坏的时候，重组大肠杆菌Nissle-HA110-120在健康或患有急性结肠炎的小鼠体内都没有迁移、克隆扩增和激活特异性CD4+T淋巴细胞的作用。

Abstract:

Abstract:It is difficult to stimulate efficient gut mucosal immune response to intestinal infection．This article critically reviews the research progressin Escherichia coli strain Nissle1917 (EcN) actingas a safe vehicle for the intestinal mucosal immunity，to restore gastrointestinal disorder and relieve ulcerative colitis． EcN is an orally administered probiotics，combining the excellent colonization and non-immunogenic character，and can be an ideal live vector candidate．This strain could be a tumor-targeted delivery of TAT-Apoptin fusion gene to colorectal cancer．In the treatment of ulcerative colitis and Crohn's disease，the recombinant strain of EcN can be used as a target therapeutics for defensins presenting．Genetically modified EcN could be an ideal carrier organism for gut-focused in situ synthesis and expression of specific localized antigen delivery into the intestine，and stimulate specific mucosal immune response． In vitro trial demonstrated that intestinal recombinant E． coli Nissle-HA110-120 has the potential to stimulate antigen specific response，but EcN itself does not induce mucosal immune response and influence peripheral tolerance to self-antigen． At the same time，there are evidences that EcN is safe．Recombinant E．coli Nissle-HA110-120 does not migrate，clonally expand and activate specific CD4 + T cells，neither in healthy mice nor in other animals with acute colitis，even when the intestinal epithelium suffer from inflammation and the barrier function of the epithelial layer being destroyed．