c-di-AMP在细菌感染与免疫中的作用

Role of c-di-AMP in bacterial infection and immunity

环二腺苷酸(Cyclic diadenosine monophosphate,c-di-AMP)是细菌中广泛存在的第二信号分子。c-di-AMP在细菌中的代谢受二腺苷酸环化酶(Diadenylatecyclase, DAC)和磷酸二酯酶(Phosphodiesterase,PDE)的精密调控。c-di-AMP不仅调节细菌生长、细胞壁稳态、离子转运等多种生理过程,而且能够被真核宿主胞内多种感应子/受体蛋白识别,从而调控抗感染免疫。细菌c-di-AMP参与调控宿主I型干扰素应答、NF-κB信号通路活性、自噬以及炎症小体应答等固有免疫应答。此外,c-di-AMP作为黏膜佐剂可诱导宿主适应性免疫。c-di-AMP被认为是一种新发现的病原体相关的分子模式(Pathogen associated molecular pattern,PAMP),已成为细菌疫苗和药物研究中的新靶点。

Cyclic diadenosine monophosphate(c-di-AMP)is a ubiquitous class of second messenger molecule in bacteria,whose metabolism is finely tuned by diadenylate cyclase(DAC)and phosphodiesterase(PDE).c-di-AMP is not only involved in many essential processes such as cell growth,cell wall homeostasis and ion transport,but also in host anti-bacterial immunity through being sensed by eukaryotic sensors/receptors of host cells.In particular,c-di-AMP has been found to play important roles in regulating host innate immunity such as type I interferon response,activation of NF-κB signal pathway,autophagy and inflammatory response.Acting as a mucosal adjuvant,c-di-AMP induces host adaptive immune response as well.Thus c-di-AMP is now considered to be a newly identified pathogen associated molecular pattern(PAMP),which becomes a new target in bacterial vaccines and drug research.