Luecke Stefanie, Paludan Søren R
Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Denmark.
Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Denmark; Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark.
Cytokine. 2017 Oct;98:4-14. doi: 10.1016/j.cyto.2016.10.003. Epub 2016 Oct 14.
Nucleic acids sensors of the innate immune system recognize various RNA and DNA structures during infection to induce transcription of interferon and pro-inflammatory cytokines and activation of inflammasomes. Cytosolic RNA is recognized by RIG-I and MDA5, while intracellular DNA is sensed among others by cGAS, AIM2, IFI16 and RNA polymerase III. The diversity of nucleic acid species produced during infection in the cytosol and nucleus and the limited chemical differences between self and non-self nucleic acids challenge the host's innate pattern recognition system to ensure reliable sensing while avoiding immune activation by self nucleic acids. We review the molecular characteristics of intracellular nucleic acid sensor ligands, the structural basis of the binding preferences of the sensors, the identity and origin of immunostimulatory nucleic acid species during infection, the influence of intracellular localization of the sensor on immune activation, and the ability of viruses to use the ligand specificity of the sensors to evade recognition.
先天性免疫系统的核酸传感器在感染期间识别各种RNA和DNA结构，以诱导干扰素和促炎细胞因子的转录以及炎性小体的激活。胞质RNA由RIG-I和MDA5识别，而细胞内DNA则由cGAS、AIM2、IFI16和RNA聚合酶III等识别。感染期间在细胞质和细胞核中产生的核酸种类的多样性以及自身与非自身核酸之间有限的化学差异，对宿主的先天性模式识别系统提出了挑战，以确保可靠的传感，同时避免自身核酸引发免疫激活。我们综述了细胞内核酸传感器配体的分子特征、传感器结合偏好的结构基础、感染期间免疫刺激性核酸种类的身份和来源、传感器细胞内定位对免疫激活的影响，以及病毒利用传感器配体特异性逃避识别的能力。
