STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00641085" target="_blank" >RIV/61388963:_____/25:00641085 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/25:00641085 RIV/00216208:11310/25:10504803
Result on the web
<a href="https://doi.org/10.1038/s41420-025-02786-1" target="_blank" >https://doi.org/10.1038/s41420-025-02786-1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41420-025-02786-1" target="_blank" >10.1038/s41420-025-02786-1</a>

Result language
angličtina
Original language name
STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction
Original language description
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway senses double-stranded DNA in the cytoplasm, triggering the secretion of type I and III interferons and proinflammatory cytokines. However, cGAS-STING pathway activation by STING agonists also induces regulated cell death (RCD) in human monocytes, which is inherently linked to cytokine production. We identified that STING agonist-induced monocyte RCD integrates apoptotic (active caspase-9,8 and3/7) and pyroptotic mechanisms (active caspase-1, cleaved gasdermin-D and secreted mature interleukin-1 beta and18), whereas necroptosis is inhibited through caspase-8-mediated cleavage of receptor-interacting protein kinase 1 (RIPK1). Additionally, this RCD is accompanied by mitochondrial dysfunction, which precedes caspase activation, suggesting that mitochondrial disruption may act as both the driving mechanism and a direct outcome of cGAS-STING pathway activation via the STING-IRF3-BAX pathway. Overall, this study identifies a novel RCD process that may be described as 'pyroptotic apoptosis', providing new insights into the outcomes of cGAS-STING signalling in human monocytes.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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