Lee Myeong Sup, Kim Young-Joon
Department of Biochemistry, Yonsei University, Seoul 120-749, Republic of Korea.
Annu Rev Biochem. 2007;76:447-80. doi: 10.1146/annurev.biochem.76.060605.122847.
Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
模式识别受体（PRR）通过病原体识别启动固有免疫。血清PRR调理病原体以增强吞噬清除作用。Toll样受体（TLR）启动共同的核因子κB/激活蛋白-1（NF-κB/AP-1）以及独特的干扰素调节因子3/7（IRF3/7）信号通路，以协调固有免疫并启动针对多种病原体的适应性免疫。细胞质半胱天冬酶招募结构域（CARD）解旋酶，如视黄酸诱导基因I（RIG-I）/黑色素瘤分化相关基因5（MDA5），通过接头蛋白IPS-1诱导I型干扰素的产生来介导抗病毒免疫，而核苷酸结合寡聚化结构域（NOD）样受体主要通过激活NF-κB或炎性小体来介导抗菌免疫。树突状细胞相关C型凝集素-1（Dectin-1）对于抗真菌免疫很重要，可促进吞噬作用并激活NF-κB。潜在有害的TLR信号通路可通过负反馈机制以及抗炎因子如转化生长因子β（TGFβ）、白细胞介素（IL）-10和类固醇进行负调控。TLR-TLR和TLR-NOD的许多组合可调节炎症反应。TLR与NOD样受体家族含吡咯结构域蛋白3（NALP3）相互作用产生成熟的IL-1β。因此，PRR下游的信号通路及其相互作用以有效的方式控制免疫反应。
