Studio dell'importanza del calcio per l'attivazione canonica dello stimolatore dei geni dell'interferone (STING)

Infectious diseases have been a persistent threat throughout human history, and they continue to pose a global health challenge. Understanding the intricate relationship between infectious agents and the immune system is crucial for developing effective prevention and treatment strategies. This work focuses on the cGAS-STING pathway, an intracellular DNA sensing pathway, which is explored for its role in innate immunity. This pathway detects cytosolic DNA, particularly double-stranded DNA, and triggers the expression of type I interferons and inflammatory cytokines, eliciting innate immune responses against microbial infections. Calcium ion is involved in the regulation of many important cellular processes, and plays a role in regulating some aspects of the immune system as well. The aim of this work is to achieve a deeper understanding of the involvement of calcium in cGAS-STING pathway. We observed that calcium deprivation inhibited STING-dependent production of IFN, showing that it is needed for a proper activation. Two amino acids, D205 and E316, were identified as possible calcium binders by in silico investigation, and, in order to test their role in STING activation, mutants of the STING were produced substituting them with alanine. Overall, this study highlights the importance of calcium in the STING pathway and provides insights into the role of specific amino acids in calcium binding and subsequent pathway activation.