Vaccine & Infectious Disease Organization-International Vaccine Center (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3, Canada.
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr. Saskatoon, Saskatoon, SK, S7N 5B4, Canada.
Cell Tissue Res. 2018 Apr;372(1):1-11. doi: 10.1007/s00441-017-2767-9. Epub 2018 Jan 12.
Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be localized to the endosomes. However, continued research in this area shows that TLR localization may be altered across cell-types, and in response to stimulation, age or disease. Mucosal surfaces must remain tolerant to the commensal flora and thus intracellular or basal lateral localization of TLRs at mucosal surfaces may be necessary to prevent induction of an inflammatory response to commensal flora while still allowing the possibility for the receptors to prime an immune response when a pathogen has crossed the epithelial barrier. Here, we highlight the research specifying 'non-canonical' localization of TLRs in human and animal mucosal tissues and blood-derived cells, while excluding cultured polarized immortalized cells. Reports that only indicate TLR gene/protein expression and/or responsiveness to agonists have been excluded unless the report also indicates surface/intracellular distribution in the cell. Understanding the tissue- and species-specific localization of these specific pattern recognition receptors will lead to a greater appreciation of the way in which TLR ligands promote innate immunity and influence the adaptive immune response. A more comprehensive understanding of this information will potentially aid in the exploitation of the therapeutic or adjuvant potential of selectively localized TLRs and in opening new perspectives in understanding the basis of immunity.
Toll 样受体（TLR）1、2、4、5 和 6 最初被描述为仅表达于细胞表面，而 TLR3、7、8 和 9 则被认为位于内体中。然而，该领域的进一步研究表明，TLR 的定位可能会在细胞类型之间发生改变，并且会对刺激、年龄或疾病产生反应。黏膜表面必须对共生菌群保持耐受，因此，在黏膜表面 TLR 的细胞内或基底侧定位可能是必需的，以防止对共生菌群产生炎症反应，同时仍然允许受体在病原体穿过上皮屏障时启动免疫反应的可能性。在这里，我们重点介绍了在人类和动物黏膜组织和血液来源的细胞中指定“非典型”TLR 定位的研究，同时排除了培养的极化永生化细胞。除非报告还表明细胞中的表面/细胞内分布，否则仅指示 TLR 基因/蛋白表达和/或对激动剂的反应的报告将被排除。了解这些特定模式识别受体的组织和物种特异性定位将有助于更好地理解 TLR 配体如何促进先天免疫以及影响适应性免疫反应。更全面地了解这些信息可能有助于利用选择性定位 TLR 的治疗或佐剂潜力，并为理解免疫基础开辟新的视角。
