Rune Hartmann says: Balancing pro-inflammatory and antiviral responses during a viral infection is a key challenge for our immune system and a major determinant of our ability to survive an infection. The pro-inflammatory responses are largely driven by the NFκB signaling pathway but determining the molecular mechanism whereby viral infections induce NFκB signaling and thereby inflammation has proven difficult in mammals. We recently discovered that the STING – NFκB axis represents an evolutionarily conserved antiviral pathway present in all metazoans. In mammals, the NFκB pathway has a dual function and is also required in developmental processes, which makes it difficult to study. In contrast to mammals, flies contain a NFκB transcription factor called Relish, which is required for the immune response, but apparently no function outside immunity. This opens a unique opportunity to use the power of the Drosophila model organism for characterizing the role of the STING – NFκB signaling axis in antiviral immunity and then translate those findings back in the mammalian system. We aim to use the powerful biochemical and genetic tools as well as unbiased screening approaches available in Drosophila to identify key components of the STING – NFκB axis. Our proposed work will allow us to understand how NFκB drives a pro-inflammatory signal and how the resulting inflammation creates significant pathology during viral infection in humans. Knowledge, which may prove critical to develop novel therapeutic strategies for specific targeting of the STING – NFκB signaling axis to lower inflammation in patients.
Rune Hartmann is Professor and Group Leader at the Department of Molecular Biology and Genetics, Aarhus University.