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

摘要:

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(Diadenylate cyclase，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。

Abstract:

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.