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Toll样受体9激动剂:家畜的免疫机制及治疗潜力

TLR9 agonists: immune mechanisms and therapeutic potential in domestic animals.

作者信息

Mutwiri George

机构信息

VIDO/International Vaccine Center & School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada.

出版信息

Vet Immunol Immunopathol. 2012 Jul 15;148(1-2):85-9. doi: 10.1016/j.vetimm.2011.05.032. Epub 2011 Jun 6.

DOI:10.1016/j.vetimm.2011.05.032
PMID:21700345
Abstract

Toll like receptors (TLRs) are transmembrane glycoproteins that recognize conserved microbial molecules. Engagement of TLRs activates innate and adaptive immunity. TLR-mediated activation of immune cells results in upregulation of cytokines, chemokines and costimulatory molecules. These early innate responses control pathogen spread and initiates adaptive immune responses. Synthetic CpG oligodeoxynucleotides (ODN), agonists for TLR9, had shown great promise as immunotherapeutic agents and vaccine adjuvants in laboratory animal models of infectious disease, allergy and cancer. However, it has become apparent that CpG ODN are less potent immune activators in domestic animals and humans. The disparity in immune responses between rodents and mammals has been mainly attributed to differences in cellular expression of TLR9 in the various species. In this article, our current understanding of the immune mechanisms, as well as the potential applications of CpG ODN will be reviewed, with particular emphasis on domestic animals.

摘要

Toll样受体(TLRs)是识别保守微生物分子的跨膜糖蛋白。TLRs的激活可启动固有免疫和适应性免疫。TLR介导的免疫细胞激活会导致细胞因子、趋化因子和共刺激分子的上调。这些早期的固有免疫反应可控制病原体传播并启动适应性免疫反应。合成的CpG寡脱氧核苷酸(ODN)作为TLR9的激动剂,在传染病、过敏和癌症的实验动物模型中,作为免疫治疗剂和疫苗佐剂显示出巨大的潜力。然而,很明显,CpG ODN在家畜和人类中作为免疫激活剂的效力较低。啮齿动物和哺乳动物之间免疫反应的差异主要归因于不同物种中TLR9的细胞表达差异。在本文中,我们将综述目前对免疫机制的理解以及CpG ODN的潜在应用,尤其侧重于家畜。

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