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

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.