TY  - JOUR
AU  - Smarduch, Steve
AU  - Moreno-Velasquez, Sergio David
AU  - Ilic, Doroteja
AU  - Dadsena, Shashank
AU  - Morant, Ryan
AU  - Ciprinidis, Anja
AU  - Pereira, Gislene
AU  - Binder, Marco
AU  - García-Sáez, Ana J
AU  - Acebrón, Sergio P
TI  - A novel biosensor for the spatiotemporal analysis of STING activation during innate immune responses to dsDNA.
JO  - The EMBO journal
VL  - 44
IS  - 7
SN  - 0261-4189
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2025-00411
SP  - 2157-2182
PY  - 2025
N1  - 2025 Apr;44(7):2157-2182
AB  - The cGAS-STING signalling pathway has a central role in the innate immune response to extrinsic and intrinsic sources of cytoplasmic dsDNA. At the core of this pathway is cGAS-dependent production of the intra- and extra-cellular messenger cGAMP, which activates STING and leads to IRF3-dependent expression of cytokines and interferons. Despite its relevance to viral and bacterial infections, cell death, and genome instability, the lack of specific live-cell reporters has precluded spatiotemporal analyses of cGAS-STING signalling. Here, we generate a fluorescent biosensor termed SIRF (STING-IRF3), which reports on the functional interaction between activated STING and IRF3 at the Golgi. We show that cells harbouring SIRF react in a time- and concentration-dependent manner both to STING agonists and to microenvironmental cGAMP. We demonstrate that the new biosensor is suitable for single-cell characterisation of immune responses to HSV-1 infection, mtDNA release upon apoptosis, or other sources of cytoplasmic dsDNA. Furthermore, our results indicate that STING signalling is not activated by ruptured micronuclei, suggesting that other cytosolic pattern recognition receptors underlie the interferon responses to chromosomal instability.
KW  - Biosensor (Other)
KW  - Innate Immune Response (Other)
KW  - Micronuclei (Other)
KW  - cGAMP (Other)
KW  - cGAS-STING Signalling (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39984755
DO  - DOI:10.1038/s44318-025-00370-y
UR  - https://inrepo02.dkfz.de/record/299001
ER  -