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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/67985823:_____/25:00641085 RIV/00216208:11310/25:10504803

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Death Discovery

ISSN

2058-7716

e-ISSN

2058-7716

Svazek periodika

11

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

494

Kód UT WoS článku

001605296600003

EID výsledku v databázi Scopus

2-s2.0-105020745590