Fan Xiaojiao, Jiao Lianying, Jin Tengchuan
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Front Microbiol. 2022 Jan 25;12:809412. doi: 10.3389/fmicb.2021.809412. eCollection 2021.
The innate immune system defenses against pathogen infections via patten-recognition receptors (PRRs). PRRs initiate immune responses by recognizing pathogen-associated molecular patterns (PAMPs), including peptidoglycan, lipopolysaccharide, and nucleic acids. Several nucleic acid sensors or families have been identified, such as RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), cyclic GMP-AMP synthase (cGAS), and PYHIN family receptors. In recent years, the PYHIN family cytosolic DNA receptors have increased attention because of their important roles in initiating innate immune responses. The family members in humans include Absent in melanoma 2 (AIM2), IFN-γ inducible protein 16 (IFI16), interferon-inducible protein X (IFIX), and myeloid cell nuclear differentiation antigen (MNDA). The PYHIN family members are also identified in mice, including AIM2, p202, p203, p204, and p205. Herein, we summarize recent advances in understanding the activation and immune regulation mechanisms of the PYHIN family during microbial infection. Furthermore, structural characterizations of AIM2, IFI16, p202, and p204 provide more accurate insights into the signaling mechanisms of PYHIN family receptors. Overall, the molecular details will facilitate the development of reagents to defense against viral infections.
固有免疫系统通过模式识别受体（PRR）抵御病原体感染。PRR通过识别病原体相关分子模式（PAMP）启动免疫反应，PAMP包括肽聚糖、脂多糖和核酸。已鉴定出几种核酸传感器或家族，如视黄酸诱导基因I样受体（RLR）、Toll样受体（TLR）、环磷酸鸟苷-腺苷酸合成酶（cGAS）和PYHIN家族受体。近年来，PYHIN家族胞质DNA受体因其在启动固有免疫反应中的重要作用而受到越来越多的关注。人类中的家族成员包括黑色素瘤缺失2（AIM2）、γ干扰素诱导蛋白16（IFI16）、干扰素诱导蛋白X（IFIX）和髓细胞核分化抗原（MNDA）。PYHIN家族成员在小鼠中也有发现，包括AIM2、p202、p203、p204和p205。在此，我们总结了在理解微生物感染期间PYHIN家族的激活和免疫调节机制方面的最新进展。此外，AIM2、IFI16、p202和p204的结构特征为PYHIN家族受体的信号传导机制提供了更准确的见解。总体而言，这些分子细节将有助于开发抵御病毒感染的试剂。
