Fukata Masayuki, Vamadevan Arunan S, Abreu Maria T
Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Semin Immunol. 2009 Aug;21(4):242-53. doi: 10.1016/j.smim.2009.06.005.
Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are two major forms of innate immune sensors, which provide immediate responses against pathogenic invasion or tissue injury. Activation of these sensors induces the recruitment of innate immune cells such as macrophages and neutrophils, initiates tissue repair processes, and results in adaptive immune activation. Abnormalities in any of these innate sensor-mediated processes may cause excessive inflammation due to either hyper responsive innate immune signaling or sustained compensatory adaptive immune activation. Recent gene association studies appear to reveal strong associations of NLR gene mutations and development of several idiopathic inflammatory disorders. In contrast, TLR polymorphisms are less often associated with inflammatory disorders. Nevertheless, TLRs are up-regulated in the affected tissue of most inflammatory disorders, suggesting TLR signaling is involved in the pathogenesis of chronic and/or idiopathic inflammatory disorders. NLR signaling results in the formation of a molecular scaffold complex (termed an inflammasome) and orchestrates with TLRs to induce IL-1beta and IL-18, both of which are important mediators in the majority of inflammatory disorders. Therefore, understanding the roles of TLRs and NLRs in the pathogenesis of chronic and idiopathic inflammatory disorders may provide novel targets for the prevention and/or treatment of many common and uncommon diseases involving inflammation.
Toll样受体（TLR）和Nod样受体（NLR）是天然免疫传感器的两种主要形式，它们对病原体入侵或组织损伤提供即时反应。这些传感器的激活诱导巨噬细胞和中性粒细胞等天然免疫细胞的募集，启动组织修复过程，并导致适应性免疫激活。这些天然传感器介导的任何过程中的异常都可能由于先天性免疫信号过度反应或持续性代偿性适应性免疫激活而导致过度炎症。最近的基因关联研究似乎揭示了NLR基因突变与几种特发性炎症性疾病的发生之间存在密切关联。相比之下，TLR多态性与炎症性疾病的关联较少。然而，在大多数炎症性疾病的受累组织中TLR表达上调，提示TLR信号传导参与慢性和/或特发性炎症性疾病的发病机制。NLR信号传导导致分子支架复合物（称为炎性小体）的形成，并与TLR协同作用诱导IL-1β和IL-18，这两者在大多数炎症性疾病中都是重要的介质。因此，了解TLR和NLR在慢性和特发性炎症性疾病发病机制中的作用可能为预防和/或治疗许多常见和罕见的炎症性疾病提供新的靶点。
