Crump K E, Sahingur S E
Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA, USA Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA
J Dent Res. 2016 Jan;95(1):17-25. doi: 10.1177/0022034515609062. Epub 2015 Oct 5.
One challenge in studying chronic infectious and inflammatory disorders is understanding how host pattern recognition receptors (PRRs), specifically toll-like receptors (TLRs), sense and respond to pathogen- or damage-associated molecular patterns, their communication with each other and different components of the immune system, and their role in propagating inflammatory stages of disease. The discovery of innate immune activation through nucleic acid recognition by intracellular PRRs such as endosomal TLRs (TLR3, TLR7, TLR8, and TLR9) and cytoplasmic proteins (absent in melanoma 2 and DNA-dependent activator of interferon regulatory factor) opened a new paradigm: Nucleic acid sensing is now implicated in multiple immune and inflammatory conditions (e.g., atherosclerosis, cancer), viral (e.g., human papillomavirus, herpes virus) and bacterial (e.g., Helicobacter pylori, pneumonia) diseases, and autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis). Clinical investigations reveal the overexpression of specific nucleic acid sensors in diseased tissues. In vivo animal models show enhanced disease progression associated with receptor activation. The involvement of nucleic acid sensors in various systemic conditions is further supported by studies reporting receptor knockout mice being either protected from or prone to disease. TLR9-mediated inflammation is also implicated in periodontal diseases. Considering that persistent inflammation in the oral cavity is associated with systemic diseases and that oral microbial DNA is isolated at distal sites, nucleic acid sensing may potentially be a link between oral and systemic diseases. In this review, we discuss recent advances in how intracellular PRRs respond to microbial nucleic acids and emerging views on the role of nucleic acid sensors in various systemic diseases. We also highlight new information on the role of intracellular PRRs in the pathogenesis of oral diseases including periodontitis and oral cavity cancer, which might offer future possibilities for disease prevention and therapy.
研究慢性感染性和炎症性疾病面临的一个挑战是理解宿主模式识别受体（PRR），特别是 Toll 样受体（TLR）如何感知并响应病原体或损伤相关分子模式，它们之间以及与免疫系统不同组分的相互作用，以及它们在疾病炎症阶段传播中的作用。通过细胞内 PRR（如内体 TLR（TLR3、TLR7、TLR8 和 TLR9））和细胞质蛋白（黑色素瘤 2 缺失蛋白和干扰素调节因子的 DNA 依赖性激活剂）对核酸的识别发现先天免疫激活开启了一个新的范式：核酸传感现在涉及多种免疫和炎症病症（如动脉粥样硬化、癌症）、病毒（如人乳头瘤病毒、疱疹病毒）和细菌（如幽门螺杆菌、肺炎）疾病以及自身免疫性疾病（如系统性红斑狼疮、类风湿性关节炎）。临床研究揭示了患病组织中特定核酸传感器的过表达。体内动物模型显示与受体激活相关的疾病进展增强。报道受体敲除小鼠对疾病有保护作用或易患疾病的研究进一步支持了核酸传感器在各种全身病症中的参与。TLR9 介导的炎症也与牙周疾病有关。鉴于口腔中的持续炎症与全身疾病相关，并且口腔微生物 DNA 在远端部位被分离，核酸传感可能是口腔和全身疾病之间的潜在联系。在这篇综述中，我们讨论了细胞内 PRR 对微生物核酸反应的最新进展以及核酸传感器在各种全身疾病中作用的新观点。我们还强调了细胞内 PRR 在包括牙周炎和口腔癌在内的口腔疾病发病机制中的新信息，这可能为疾病预防和治疗提供未来的可能性。
