cGAS/STING通路的生物学功能及其在细菌感染中的作用
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河南省自然科学基金(232300421263);河南科技大学博士启动基金(13480104);国家自然科学基金(31572489)


Biological function of cGAS/STING pathway and its role in bacterial infection
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    摘要:

    先天免疫是宿主抵御外来病原体入侵的第一道防线,而模式识别受体(pattern recognition receptors, PRRs)是介导先天免疫应答关键分子。PRRs通过识别病原体相关分子模式(pathogen associated molecular patterns, PAMPs)来激活宿主先天免疫反应。二十一世纪先天免疫领域里程碑式发现-环磷酸鸟苷腺苷合成酶(cyclic GMP-AMP synthase, cGAS),cGAS在宿主先天免疫过程中发挥重要作用,通过识别外源DNA产生第二信使2′,3′-环化鸟苷酸腺苷酸(2′,3′-cyclic guanosine monophosphate adenosine monophosphate, 2′,3′-cGAMP)来介导干扰素基因刺激因子(stimulator of interferon genes, STING)的活化,从而促进下游干扰素(IFN)和其他细胞因子分泌来发挥宿主的抗病毒反应。近年研究发现,cGAS/STING通路在宿主抗细菌感染过程中发挥着重要作用,同时细菌也进化出不同机制来拮抗cGAS/STING通路。本文主要对cGAS/STING通路的生物学功能及其在细菌感染中的作用进行综述,为进一步研发新型抗菌药物提供理论参考。

    Abstract:

    Innate immunity is the first line of the host against invasion of foreign pathogens, and pattern recognition receptors (PRRs) are key receptors mediating innate immune response. PRRs activate the innate immune response of the host by recognizing pathogen associated molecular patterns (PAMPs). Among them, there is a milestone discovery in the field of DNA recognition and innate immunity in the 21st century—cyclic GMP-AMP synthase (cGAS), which plays an important role in the host innate immune process. cGAS mediates the activation of stimulator of interferon genes (STING) by recognizing foreign DNA and producing a second messenger 2′,3′-cyclic GMP-AMP (2′,3′-cGAMP), thus promoting the secretion of downstream interferon and other cytokines to play an antiviral role in the host. Recent studies have found that the cGAS/STING pathway plays an important role in the host’s resistance to bacterial infection. Meanwhile, bacteria have also evolved different mechanisms to antagonize the cGAS/STING pathway. This paper mainly reviewed the biological functions of the cGAS/STING pathway and its role in bacterial infection, providing theoretical references for the further development of new antibacterial drugs.

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陈松彪,尚珂,张春杰,丁轲,程相朝. cGAS/STING通路的生物学功能及其在细菌感染中的作用. 微生物学报, 2023, 63(7): 2595-2608

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  • 收稿日期:2022-11-15
  • 最后修改日期:2023-01-11
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  • 在线发布日期: 2023-07-05
  • 出版日期: 2023-07-04
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