Our immune system acts as a bodyguard, protecting us from getting infections from various pathogens such as viruses, bacteria, and other foreign bodies. Once the pathogen enters the body, the immune system gets activated. By the process of removing damaged tissues and ensuring tissue repair, the immune system is crucial for maintaining an optimal balance in the body.
G-protein coupled receptors (GPCRs) play an important part in immune control. They help in the activation of Guanine-nucleotide exchange factor (GEF) thereby stimulation of Heterotrimeric G proteins. Guanine nucleotide-binding G protein α subunit-interacting vesicle-associated protein GIV (also known as Girdin) is one such protein which has been known to stimulate signal transduction pathways like Akt and PI3k using coupled G proteins.
Recent research led by Prof. Pradipta Ghosh at the University of California San Diego found that GIV prevents the proper functioning of macrophages in a mouse model system lacking the GIV gene. The macrophages are the first warriors to march out in order to defend us from infectious pathogens and aid in the development of the immune reaction. The results of the study depicted a massive overreaction of the immune cells even when subjected to tiny amounts of the pathogen. Comorbidities such as colitis and sepsis aggravated the problem even further.
Upon mimicking the GIV peptide, the immune response was severely reduced. This phenomenon is similar to the ‘cytokine storm’ typically seen in Covid-19 cases. To give a gist of what happens, Covid-19 infection leads to an inflammatory response with the release of chemical molecules known as cytokines. Such heightened response is more detrimental for the body than the usual expected response in the sense that it could lead to the death of normal cells in the process. Upon further investigation, GIV was found to act through Toll-like receptor 4 (TLR4) which mainly is the reason for various immune signals during infections and the inflammatory response initiated due to that infection.
The study holds the prospect of using GIV as a regulatory mechanism to keep the immune system in check without allowing it to overload. The team plans to investigate further to determine the factors responsible for the GIV control mechanism. This will help them to understand and discover new mechanisms for controlled immune suppression in case of chronic response.
Immunosuppression has been a key area of research among scientists due to the plethora of problems being initiated due to heightened response. As excessive immune response leads to several diseases, it is highly important for the immune system to maintain homeostasis or balance in the body. Therefore, immunosuppression is an important research topic among scientists as such mechanisms can be really helpful for toning down the spike in the immune response.
