Toll样受体9激动剂的抗感染应用。
Antiinfective applications of toll-like receptor 9 agonists.
作者信息
Krieg Arthur M
机构信息
Coley Pharmaceutical Group, Inc., 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA.
出版信息
Proc Am Thorac Soc. 2007 Jul;4(3):289-94. doi: 10.1513/pats.200701-021AW.
Abstract
The innate immune system detects pathogens by the presence of highly conserved pathogen-expressed molecules, which trigger host immune defenses. Toll-like receptor (TLR) 9 detects unmethylated CpG dinucleotides in bacterial or viral DNA, and can be stimulated for therapeutic applications with synthetic oligodeoxynucleotides containing immune stimulatory "CpG motifs." TLR9 activation induces both innate and adaptive immunity. The TLR9-induced innate immune activation can be applied in the prevention or treatment of infectious diseases, and the adaptive immune-enhancing effects can be harnessed for improving vaccines. This article highlights the current understanding of the mechanism of action of CpG oligodeoxynucleotides, and provides an overview of the preclinical data and early human clinical trial results, applying these TLR9 agonists in the field of infectious diseases.
摘要
天然免疫系统通过高度保守的病原体表达分子的存在来检测病原体，这些分子触发宿主的免疫防御。Toll样受体（TLR）9可检测细菌或病毒DNA中的未甲基化CpG二核苷酸，并且可以用含有免疫刺激“CpG基序”的合成寡脱氧核苷酸进行刺激以用于治疗应用。TLR9激活可诱导先天免疫和适应性免疫。TLR9诱导的先天免疫激活可应用于传染病的预防或治疗，而适应性免疫增强作用可用于改进疫苗。本文重点介绍了目前对CpG寡脱氧核苷酸作用机制的理解，并概述了在传染病领域应用这些TLR9激动剂的临床前数据和早期人体临床试验结果。
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