Xia Pengpeng, Zhu Jun, Zhu Guoqiang
College of Veterinary Medicine, Ministry of Education Key Lab for Avian Preventive Medicine, Yangzhou University, Yangzhou 225009, China.
Wei Sheng Wu Xue Bao. 2013 Jun 4;53(6):538-44.
It is difficult to stimulate efficient gut mucosal immune response to intestinal infection. This article critically reviews the research progressin Escherichia coli strain Nisslel917 ( 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.
难以刺激肠道对感染产生有效的黏膜免疫反应。本文批判性地综述了大肠杆菌Nissle1917(EcN)作为肠道黏膜免疫的安全载体、恢复胃肠道紊乱及缓解溃疡性结肠炎方面的研究进展。EcN是一种口服益生菌,兼具良好的定植能力和非免疫原性,可成为理想的活载体候选物。该菌株可将TAT - Apoptin融合基因靶向递送至结直肠癌。在溃疡性结肠炎和克罗恩病的治疗中,EcN重组菌株可作为呈递防御素的靶向治疗剂。基因改造后的EcN可能是用于肠道原位合成和表达并向肠道递送特定局部抗原、刺激特异性黏膜免疫反应的理想载体生物。体外试验表明,肠道重组大肠杆菌Nissle - HA110 - 120有刺激抗原特异性反应的潜力,但EcN本身不会诱导黏膜免疫反应,也不会影响对外源自身抗原的外周耐受。同时,有证据表明EcN是安全的。重组大肠杆菌Nissle - HA110 - 120在健康小鼠或患有急性结肠炎的其他动物中均不会迁移、克隆扩增及激活特异性CD4 + T细胞,即使肠道上皮发生炎症且上皮层屏障功能被破坏时也是如此。