Immunological Reviews ( IF 7.5 ) Pub Date : 2020-08-27 , DOI: 10.1111/imr.12912
Thirumala-Devi Kanneganti 1
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1 INTRODUCTION
The innate immune system is the critical first line of defense against infectious and sterile insults. A cell’s ability to sense these insults relies on a series of germline‐encoded receptors, generally referred to as pattern recognition receptors (PRRs). PRRs are responsible for recognizing unique molecular patterns from microbes known as pathogen‐associated molecular patterns (PAMPs) and endogenous molecules released from damaged and dying cells known as damage‐associated molecular patterns (DAMPs). There are several different PRRs found throughout the cell, including Toll‐like receptors (TLRs), C‐type lectin receptors (CLRs), nucleotide‐binding domain, leucine‐rich repeat‐containing (or NOD‐like) receptors (NLRs), absent in melanoma 2 (AIM2), IFI16, pyrin, Z‐DNA‐binding protein 1 (ZBP1), retinoic acid‐inducible gene I (RIG‐I), MDA5, and many more. PRRs can be found on the membrane, in the cytosol, and in the nucleus. Some PRRs can induce the formation of a multiprotein complex called the inflammasome that leads to the processing and release of the proinflammatory cytokines IL‐1β and IL‐18 and cell death in the form of pyroptosis. Within the NLR family of PRRs, there are some proteins that form an inflammasome, such as NLRP1, NLRP3, and NLRC4, and some that do not, such as NLRC1 and NLRC2 (NOD1 and NOD2). AIM2 and pyrin are also well‐established as sensors that form an inflammasome. Whether they form inflammasomes or not, PRRs are each important for sensing their respective ligands and initiating signaling pathways that drive gene expression, protein production, cytokine and chemokine release, and cell death while also shaping the adaptive immune response, dictating the overall fitness of the immune system.
Within the cell, membrane‐bound PRRs are responsible for sensing external insults, while intracellular cytosolic and nuclear PRRs are essential for detecting intracellular pathogens or alterations in cellular homeostasis. In this issue of Immunological Reviews, we explore the intracellular innate immune receptors, characterizing their sensing and signaling pathways and detailing their diverse roles in health and disease. We also describe the therapeutic implications of modulating these pathways.
中文翻译：
细胞内先天免疫受体：细胞内的生命。
1 简介
先天免疫系统是抵御传染性和无菌性损伤的关键第一道防线。细胞感知这些损伤的能力依赖于一系列种系编码受体，通常称为模式识别受体（PRR）。 PRR 负责识别来自微生物的独特分子模式（称为病原体相关分子模式 (PAMP)）以及从受损和垂死细胞释放的内源分子（称为损伤相关分子模式 (DAMP)）。在整个细胞中发现了几种不同的 PRR，包括 Toll 样受体 (TLR)、C 型凝集素受体 (CLR)、核苷酸结合域、富含亮氨酸重复序列（或 NOD 样）受体 (NLR)、黑色素瘤 2 (AIM2)、IFI16、pyrin、Z-DNA 结合蛋白 1 (ZBP1)、视黄酸诱导基因 I (RIG-I)、MDA5 等中不存在。 PRR 可以在细胞膜、细胞质和细胞核中找到。一些 PRR 可以诱导称为炎性小体的多蛋白复合物的形成，导致促炎细胞因子 IL-1β 和 IL-18 的加工和释放以及细胞焦亡形式的死亡。在 PRR 的 NLR 家族中，有些蛋白质可形成炎症小体，例如 NLRP1、NLRP3 和 NLRC4，而另一些则不形成炎症小体，例如 NLRC1 和 NLRC2（NOD1 和 NOD2）。 AIM2 和pyrin 也是公认的形成炎症小体的传感器。无论它们是否形成炎症小体，PRR 对于感知各自的配体并启动驱动基因表达、蛋白质产生、细胞因子和趋化因子释放以及细胞死亡的信号传导途径都很重要，同时还塑造适应性免疫反应，决定机体的整体适应性。免疫系统。
在细胞内，膜结合的 PRR 负责感知外部损伤，而细胞内的胞质和核 PRR 对于检测细胞内病原体或细胞稳态的改变至关重要。在本期《免疫学评论》中，我们探讨了细胞内先天免疫受体，描述了它们的传感和信号传导途径，并详细说明了它们在健康和疾病中的不同作用。我们还描述了调节这些途径的治疗意义。
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