c-di-AMP

C-di-AMP is a STING agonist, which binds to the transmembrane protein STING, thereby activating the TBK3-IRF3 signaling pathway, subsequently triggering the production of type I IFN and TNF. c-di-AMP serves as a second messenger in bacteria, primarily regulating cell growth, survival, and virulence in Gram-positive bacteria, and also modulates the host immune response. As an effective mucosal adjuvant, c-di-AMP stimulates both humoral and cellular responses[1-5]. C-di-AMP have been utilized as vaccine adjuvants for influenza and hepatitis C.Citation[6].

Combination of c-di-AMP(5 ug/ml;48h) with radiation promotes the secretion of type I IFN and ISG levels in BMDCs[7].

C-di-AMP(25ug;i.p;3 times) can synergistically enhance the antitumor effects of Radiotherapy (RT)-associated dsDNA by promoting IFN-β production and CD8+ cytolytic T cell activation in a cGAS- and STING-dependent manner in mice[7].

References:
[1]. Jenal U, Reinders A, et,al.Cyclic di-GMP: second messenger extraordinaire. Nat Rev Microbiol. 2017 May;15(5):271-284. doi: 10.1038/nrmicro.2016.190. Epub 2017 Feb 6. PMID: 28163311.
[2]. Fahmi T, Port GC, et,al.c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria. Genes (Basel). 2017 Aug 7;8(8):197. doi: 10.3390/genes8080197. PMID: 28783096; PMCID: PMC5575661.
[3]. Ning H, Wang L, et,al. Recombinant BCG With Bacterial Signaling Molecule Cyclic di-AMP as Endogenous Adjuvant Induces Elevated Immune Responses After Mycobacterium tuberculosis Infection. Front Immunol. 2019 Jul 3;10:1519. doi: 10.3389/fimmu.2019.01519. PMID: 31333655; PMCID: PMC6618344.
[4]. Ebensen T, Delandre S, et,al. The Combination Vaccine Adjuvant System Alum/c-di-AMP Results in Quantitative and Qualitative Enhanced Immune Responses Post Immunization. Front Cell Infect Microbiol. 2019 Feb 19;9:31. doi: 10.3389/fcimb.2019.00031. PMID: 30838180; PMCID: PMC6390046.
[5]. Sanchez MV, Ebensen T, et,al. Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge. PLoS One. 2014 Aug 20;9(8):e104824. doi: 10.1371/journal.pone.0104824. PMID: 25140692; PMCID: PMC4139298.
[6]. Yin W, Cai X, et,al. A decade of research on the second messenger c-di-AMP. FEMS Microbiol Rev. 2020 Nov 24;44(6):701-724. doi: 10.1093/femsre/fuaa019. PMID: 32472931; PMCID: PMC7850090.
[7]. Li Z, Zhang Y, et,al. Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling. Gut Microbes. 2022 Jan-Dec;14(1):2119055. doi: 10.1080/19490976.2022.2119055. PMID: 36093568; PMCID: PMC9467592.

C-di-AMP是STING(刺激内质网的蛋白)的激动剂,通过与该跨膜蛋白结合,激活TBK3-IRF3信号通路,进而引发I型IFN和TNF的产生。c-di-AMP在细菌中作为第二信使发挥作用,主要调节革兰氏阳性菌的细胞生长、存活和毒力,并调节宿主的免疫反应。作为有效的粘膜佐剂,c-di-AMP可以刺激体液和细胞反应[1-5]。C-di-AMP已被用作流感和丙型肝炎的疫苗佐剂[6]。

C-di-AMP(5 ug/ml;48h)联合放疗可促进BMDCs分泌I型IFN和ISG[7]。

C-di-AMP(25ug;i.p;3 times) 可以协同增强RT相关dsDNA的抗肿瘤作用,通过cGAS-和STING-依赖的方式促进小鼠IFN-β的产生和CD8+细胞溶解T细胞的活化[7]。