Mitchell Jane A, Paul-Clark Mark J, Clarke Graham W, McMaster Shaun K, Cartwright Neil
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Cardiac Medicine, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
J Endocrinol. 2007 Jun;193(3):323-30. doi: 10.1677/JOE-07-0067.
Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line-encoded receptors, including transmembrane Toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine-rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular patterns (PAMPs) results in genomic responses in host cells involving activation transcription factors and the induction of genes. There are now at least 10 TLRs in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via interactions with adaptor proteins including MyD88 and toll-receptor associated activator of interferon (TRIF). NOD signalling is via the inflammasome and involves activation of Rip-like interactive clarp kinase (RICK). Bacterial lipopolysaccharide (LPS) from Gram-negative bacteria is the best-studied PAMP and is activated by or 'sensed' by TLR4. Lipoteichoic acid (LTA) from Gram-positive bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades, although activation of either results in symptoms of sepsis and shock. This review describes the rapidly expanding field of pathogen-sensing receptors and uses LPS and LTA as examples of how these pathways parallel and diverge from each other. The role of pathogen-sensing pathways in disease is also discussed.
病原体由模式识别受体（PRR）感知，PRR是种系编码的受体，包括跨膜Toll样受体（TLR）和含有富含亮氨酸重复序列（NLR）的胞质核苷酸寡聚化结构域（NOD）蛋白。特定病原体相关分子模式（PAMP）激活PRR会导致宿主细胞发生基因组反应，包括激活转录因子和诱导基因表达。目前人类至少有10种TLR，小鼠有13种，还有2种NLR（NOD1和NOD2）。TLR信号传导是通过与包括髓样分化因子88（MyD88）和干扰素Toll样受体相关激活剂（TRIF）在内的衔接蛋白相互作用来实现的。NOD信号传导是通过炎性小体进行的，涉及Rip样相互作用的丝氨酸/苏氨酸激酶（RICK）的激活。革兰氏阴性菌的细菌脂多糖（LPS）是研究得最透彻的PAMP，可被TLR4激活或“感知”。革兰氏阳性菌的脂磷壁酸（LTA）由TLR2感知。TLR4和TLR2具有不同的信号级联反应，尽管两者的激活都会导致败血症和休克症状。这篇综述描述了病原体感知受体这一迅速发展的领域，并以LPS和LTA为例说明这些途径如何相互平行和不同。还讨论了病原体感知途径在疾病中的作用。
