Monash University scientists have made a groundbreaking discovery regarding the immune system’s role in controlling the body’s inflammatory response to infections. This discovery could potentially lead to more targeted therapies for various inflammatory conditions, including neuroinflammatory disease and autoimmunity.
The body’s innate immune system is its primary defense against pathogens, where proteins within the immune system recognize foreign bodies such as viruses and bacteria, then respond by initiating an inflammatory immune response to destroy the pathogen.
For optimal host protection against infections, a tightly controlled inflammatory response is necessary, where it turns on and off precisely. However, in some cases, these pathways may remain switched on and not turn off, resulting in neurodegenerative and autoimmune diseases.
In a study published in The EMBO Journal, researchers investigated the intricate chain of events involved in the inflammatory response mediated by Stimulator of Interferon Genes (STING), a vital protein within the innate immune system.
Dr. Dominic De Nardo, Senior Researcher at the Monash Biomedicine Discovery Institute (BDI), explained the significance of their findings.
“The innate immune system has been part of our evolutionary history for a long time and is highly resilient. Its various components function in detecting pathogens, initiating an inflammatory immune response to clear the threat, and signaling to the system that it’s time to stop the inflammation.”
The primary focus of my team is to investigate the inflammatory responses triggered by a crucial innate immune receptor called Stimulator of Interferon Genes (STING), which can alert the body to pathogenic danger or be activated by misplaced factors within our body.
Our aim is to control and halt detrimental inflammation in diseases caused by unwarranted activation and/or ineffective termination of STING. We intend to further our research on human immune cells and pre-clinical studies.
As the first author and a recently graduated Ph.D. student, I, Dr. Kate Balka, highlighted that our team aimed to understand how STING immune responses are regulated to ensure adequate host immunity. STING responses are critical for clearing pathogens, but uncontrolled STING activity leads to several inflammatory conditions such as autoinflammatory, autoimmune, and neurodegenerative diseases. Therefore, we aimed to answer the question, “how is STING turned off?”
Our research determined the precise mechanisms regulating the termination of STING responses. We discovered the endosomal sorting complex required for transport (ESCRT), which packages STING into small compartments for lysosomal degradation.
By understanding this critical step in STING regulation, we can explore new therapeutic targets for potential treatment of STING-related pathologies.