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细菌环二核苷酸与cGAS-cGAMP-STING通路：在牙周炎中起作用？

Bacterial Cyclic Dinucleotides and the cGAS-cGAMP-STING Pathway: A Role in Periodontitis?

作者信息

Elmanfi Samira, Yilmaz Mustafa, Ong Wilson W S, Yeboah Kofi S, Sintim Herman O, Gürsoy Mervi, Könönen Eija, Gürsoy Ulvi K

机构信息

Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland.

Department of Periodontology, Faculty of Dentistry, Biruni University, 34010 Istanbul, Turkey.

出版信息

Pathogens. 2021 May 30;10(6):675. doi: 10.3390/pathogens10060675.

DOI:10.3390/pathogens10060675
PMID:34070809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8226932/
Abstract

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides-including c-di-GMP, c-di-AMP, and cGAMP-of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms "STING", "TBK 1", "IRF3", and "cGAS"-alone, or together with "periodontitis". Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

摘要

宿主细胞可通过关键且必需的先天性免疫信号衔接分子——信号转导及转录激活因子（STING），识别胞质双链DNA以及入侵微生物的内源性第二信使（如环二鸟苷酸、环二腺苷酸和环鸟苷酸-腺苷酸）。这种识别激活先天性免疫系统，导致I型干扰素和促炎细胞因子的产生。在本综述中，我们（1）关注细菌环二核苷酸以及STING/TBK1/IRF3通路在牙周病发病机制和牙周免疫反应调节中的可能作用，（2）回顾并讨论作为免疫反应调节剂的STING通路激活剂和抑制剂及其在治疗牙周炎中的潜在效用。我们使用“STING”“TBK 1”“IRF3”和“cGAS”等术语单独或与“牙周炎”一起在PubMed/Medline、Scopus和Web of Science数据库中进行检索。目前的研究为将靶向STING通路的分子用作抗癌治疗的一部分以及抗微生物感染疫苗佐剂提供了证据；然而，STING/TBK1/IRF3通路在牙周病发病机制中的作用仍未被发现。了解环二核苷酸对先天性免疫反应的刺激为牙周病学中的宿主调节疗法开辟了一条新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/4874364574ac/pathogens-10-00675-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/c3c6eb73535e/pathogens-10-00675-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/4874364574ac/pathogens-10-00675-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/c3c6eb73535e/pathogens-10-00675-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/b20801eb0810/pathogens-10-00675-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cdd/8226932/9434e1d7cea6/pathogens-10-00675-g003.jpg
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本文引用的文献

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MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway.MYSM1通过抑制cGAS-STING途径来抑制先天性免疫和自身免疫。
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