细菌c-di-AMP在宿主免疫中的作用研究  

Advances in Research on the Role of Bacterial c-di-AMP in Host Immunity

作　　者：吴沁蕊 彭显 周学东[1] WU Qin-rui;PENG Xian;ZHOU Xuedong(State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Dental and Endodontic Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心四川大学华西口腔医院牙体牙髓病科,成都610041

出　　处：《四川大学学报（医学版）》2022年第6期1098-1103,共6页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.32070120、No.81991500和No.81991501)资助。

摘　　要：环状二聚腺苷-3′,5′-单磷酸(cyclic diadenosine monophosphate,c-di-AMP)是细菌和古细菌中新发现的第二信使。通过直接与靶蛋白结合或影响靶蛋白表达,c-di-AMP调节多种细菌的生理功能,包括维持渗透压、平衡中枢代谢、监测DNA损伤以及控制生物膜和孢子形成。作为一种新型病原体相关分子模式与宿主模式识别受体结合,通过激活干扰素基因刺激蛋白(stimulator of interferon genes,STING),诱导环磷酸鸟苷-磷酸腺苷合酶(cyclic GMP-AMP synthase,cGAS)-STING信号轴产生Ⅰ型干扰素,并通过核因子-κB信号通路促进炎症因子分泌,在宿主对细菌感染及肿瘤的免疫中发挥重要作用。因其良好的免疫原性,c-di-AMP可作为免疫佐剂为疫苗的研发提供新的靶点。然而,对c-di-AMP在宿主免疫中的具体作用机制有待进一步探索。本文介绍了c-di-AMP的结构及生物学特性,总结了c-di-AMP对宿主免疫应答调控的可能机制,同时跟进其作为免疫佐剂应用于临床的治疗新进展。研究c-di-AMP的功能及对宿主免疫应答的作用机制可为临床上解决细菌耐药、感染控制、肿瘤防治以及疫苗开发提供新的思路。Cyclic dimeric adenosine 3′,5′-monophosphate(c-di-AMP)is a newly-discovered second messenger in bacteria and archaea.By directly binding to or affecting the expression of target proteins,c-di-AMP regulates the physiological functions of bacteria,including maintaining osmotic pressure,balancing central metabolism,monitoring DNA damage,and controlling biofilm and spore formation.As a new pathogen-associated molecular pattern(PAMP),it binds to the host pattern recognition receptor(PRR),induces cyclic GMP-AMP synthase(cGAS)-STING signal axis to produce typeⅠinterferon by activating the stimulator of interferon genes(STING),and promotes the secretion of inflammatory factors through nuclear factorκB(NF-κB)signaling pathway,thereby playing an important role in host immunity to bacterial infection and tumorigenesis.Due to its immunogenicity,c-di-AMP could be used as an immune adjuvant to provide new targets for the development of vaccines.However,the specific mechanism of action of c-di-AMP in host immunity awaits further exploration.Herein,we presented the structure and biological characteristics of c-di-AMP,and summarized the possible mechanism of c-di-AMP’s regulation of host immune response.In addition,we also reported the latest findings on using c-di-AMP as an immune adjuvant in clinical treatment.Research on the function of c-di-AMP and its mechanism of action on host immune response provides new ideas for finding clinical solutions to bacterial resistance,infection control,tumor prevention,and vaccine development in the future.

关 键 词：c-di-AMP 第二信使 细菌感染 肿瘤 免疫佐剂 

分 类 号：R392[医药卫生—免疫学]