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The microbiome and cytosolic innate immune receptors.
Immunological Reviews ( IF 7.5 ) Pub Date : 2020-07-13 , DOI: 10.1111/imr.12901
Timur Liwinski 1, 2 , Danping Zheng 1, 3 , Eran Elinav 1, 4
Affiliation  

The discovery of innate immune sensors (pattern recognition receptors, PRRs) has profoundly transformed the notion of innate immunity, in providing a mechanistic basis for host immune interactions with a wealth of environmental signals, leading to a variety of immune‐mediated outcomes including instruction and activation of the adaptive immune arm. As part of this growing understanding of host‐environmental cross talk, an intimate connection has been unveiled between innate immune sensors and signals perceived from the commensal microbiota, which may be regarded as a hub integrating a variety of environmental cues. Among cytosolic PRRs impacting on host homeostasis by interacting with the commensal microbiota are nucleotide‐binding domain, leucine‐rich repeat‐containing protein receptors (NLRs), together with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)–like receptors (ALRs). NLR sensors have been a particular focus of research, and some NLRs have emerged as key orchestrators of inflammatory responses and host homeostasis. Some NLRs achieve this through the formation of cytoplasmic multiprotein complexes termed inflammasomes. More recently discovered PRRs include retinoic acid‐inducible gene‐I (RIG‐I)–like receptors (RLRs), cyclic GMP‐AMP synthase (cGAS), and STING. In the present review, they summarize recent advancements in knowledge on structure and function of cytosolic PRRs and their roles in host‐microbiota cross talk and immune surveillance. In addition, we discuss their relevance for human health and disease and future therapeutic applications involving modulation of their activation and signaling.

中文翻译:

微生物组和细胞溶质先天免疫受体。

先天免疫传感器(模式识别受体,PRRs)的发现深刻地改变了先天免疫的概念,为宿主免疫与大量环境信号的相互作用提供了机制基础,导致了各种免疫介导的结果,包括指令和适应性免疫臂的激活。作为对宿主 - 环境串扰的日益了解的一部分,先天免疫传感器与从共生微生物群感知的信号之间的密切联系已经揭晓,共生微生物群可被视为整合各种环境线索的枢纽。在通过与共生微生物群相互作用影响宿主稳态的细胞质 PRR 中,有核苷酸结合域、富含亮氨酸重复序列的蛋白质受体 (NLR)、连同许多细胞质 DNA 传感器和黑色素瘤 (AIM) 样受体 (ALR) 中缺失的家族。NLR 传感器一直是研究的一个特别焦点,一些 NLR 已成为炎症反应和宿主体内平衡的关键协调者。一些 NLR 通过形成称为炎性体的细胞质多蛋白复合物来实现这一点。最近发现的 PRR 包括视黄酸诱导基因 I (RIG-I) 样受体 (RLR)、环 GMP-AMP 合酶 (cGAS) 和 STING。在本综述中,他们总结了关于胞质 PRR 结构和功能的最新进展及其在宿主微生物群串扰和免疫监视中的作用。此外,我们讨论了它们与人类健康和疾病的相关性以及涉及调节它们的激活和信号传导的未来治疗应用。
更新日期:2020-08-28
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