Science: Studies Revealed a New Innate Immunity Sensor of Enzyme and Cell Signaling Pathway
Scientists have known the immune-boosting response of DNA for a long time, but the specific mechanism of the underlying response is unknown. The studies solved the longstanding puzzle by means of a special biochemical approach.
The approach is quantitative mass spectrometry which adopts a modern technology with classical protein purification to identify the mysterious compound at the clou of the discovered process.
Two studies conducted among multiple centers have identified a new enzyme—cyclic GMP-AMP synthase (cGAS) that acts as a sensor of innate immunity and a fresh cell signaling pathway. cGAS sounds like a cellular alarm when it encounters DNA in the cytoplasm. Innate immunity is our body’s first line of defense against invaders; the fresh pathway detects foreign DNA or even host DNA once these DNA cross the “normal line”. Foreign DNA in the cytoplasm is a sign of attack by a virus, bacteria, or parasite. Host DNA that somehow leaks into the cytoplasm can trigger autoimmune conditions, like lupus, Sjogren’s syndrome, and Aicardi-Goutiere’s syndrome in humans.
Moreover, their studies discovered that the process will recruit a naturally forming compound—cyclic GMP-AMP (cGAMP) which is never previously found in humans or other multi-cellular organisms. After cGAS detects and binds to the DNA, it catalyzes the formation of cGAMP. The cGAMP functions as a second messenger that binds to an adaptor protein called STING, which activates a cell signaling cascade that in turn produces agents of inflammation: interferons and cytokines.
If without surprise, DNA is contained within membrane-bound structures, such as the nucleus and mitochondria that are suspended within the cell’s cytoplasm. DNA in the cytoplasm is a danger signal that triggers immune responses, including the production of type-1 interferons (IFN).
In normal conditions, this pathway is important for immune defense against infections by microbial pathogens. However, when the immune system turns against host DNA, it can cause autoimmune diseases, while this discovery of cGAS as the DNA sensor provides an attractive target for the development of new drugs that might treat autoimmune diseases.
Tags: Innate Immunity Sensor of Enzyme, Signaling Pathway, GMP-AMP Synthase, Cyclic GMP-AMP