How the Immune System Recognizes DNA as a Threat
Recent research has shed light on the mechanisms by which the immune system identifies double-stranded DNA (dsDNA) as a potential danger. This discovery is critical, as the presence of dsDNA in the plasma of a cell can indicate viral or bacterial infection, or cellular malfunction, given that DNA is typically confined to the nucleus or mitochondria.
On March 14, a day commemorating the influential immunologist and Nobel laureate Paul Ehrlich, the prestigious Paul-Ehrlich-und-Ludwig-Darmstaedter Prize was awarded to three distinguished researchers. The prize, valued at EUR120,000, is recognized as Germany's most prominent medical award. This year, the awardees included Professor Dr. Andrea Ablasser from Germany, Professor Dr. Glen Barber from the UK and USA, and Professor Dr. Zhijian Chen from China and the USA.
These scholars have made significant contributions to understanding a vital aspect of the innate immune system that becomes activated upon the detection of dsDNA in the cell's plasma. The initial breakthrough came from Glen Barber, who isolated a protein embedded in the endoplasmic reticulum (ER). This protein, known as STING (Stimulator of Interferon Genes), plays a crucial role in inducing the production of interferon-? and other cytokines as part of the innate immune response following DNA virus infections. Interestingly, STING does not directly interact with DNA, indicating the existence of an additional sensor.
Zhijian Chen was instrumental in identifying this sensor and its signaling molecule that activates STING. He discovered a unique cyclic dinucleotide called cGAMP, which is specific to this signaling pathway. The enzyme responsible for synthesizing cGAMP from ATP and GTP, now termed cGAS (cyclic GMP-AMP synthase), was also isolated by Chen. Professor Andrea Ablasser previously elucidated the biosynthesis of cGAMP, a contribution that earned her the Paul-Ehrlich-und-Ludwig-Darmstaedter Young Talent Award in 2014.
These fundamental discoveries hold promise for medical applications. Agonists targeting this signaling pathway could enhance treatment options for cancer, while antagonists may be developed for managing chronic inflammatory conditions.