Cyclic Dinucleotides and the Innate Immune Response

Cyclic Dinucleotides and the Innate Immune Response

Cyclic dinucleotides (CDNs) have been previously recognized as important secondary signaling molecules in bacteria and, more recently, in mammalian cells. In the former case, they represent secondary messengers affecting numerous responses of the prokaryotic cell, whereas in the latter, they act as agonists of the innate immune response. Remarkable new discoveries have linked these two patterns...

Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides

The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3'5'-3'5' cyclic GMP-AMP (3'3' cGAMP) produced by Vibrio cholerae and metazoan second messenger 2'5'-3'5' Cyclic GMP-AMP (2'3' cGAMP). Analysis of single nu...

Cyclic Dinucleotides Trigger ULK1 (ATG1) Phosphorylation of STING to Prevent Sustained Innate Immune Signaling

Activation of the stimulator of interferon genes (STING) pathway by microbial or self-DNA, as well as cyclic dinucleotides (CDNs), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent proinflammatory disease by mechanisms that remain unknown. We d...

P38: The Immunoregulatory Effect of Cyclic Dinucleotides on Human Immune Cells

In multiple sclerosis (MS) beneficial effects have been assigned to the interferon (IFN)-I subclass IFN-ß, making its administration a first-line disease-modifying treatment in MS. IFN-I responses can be induced by cyclic-dinucleotide (CDN) triggered activation of Stimulator-of-interferon-genes (STING) and have essential immunomodulatory effects. A beneficial effect of STING activation on...

Induction of Innate Immune Response