STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis

0556396 - ÚOCHB 2023 RIV US eng J - Journal Article
Pimková Polidarová, Markéta - Břehová, Petra - Dejmek, Milan - Birkuš, Gabriel - Brázdová, Andrea
STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis.
ACS Infectious Diseases. Roč. 8, č. 3 (2022), s. 463-471. ISSN 2373-8227
R&D Projects: GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963
Keywords : STING * cGAS-STING pathway * apoptosis * monocytes * proinflammatory cytokines * interferons
OECD category: Biochemistry and molecular biology
Impact factor: 5.3, year: 2022
Method of publishing: Limited access
https://doi.org/10.1021/acsinfecdis.1c00554

The cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway plays a crucial role in inducing an antiviral and antitumor immune response. We studied the effects of synthetic STING agonists on several immune populations and related cytokine production. In comparison with the toll-like receptor 7 (TLR7) agonist, STING agonists induced secretion of a broader proinflammatory cytokine spectrum. Unlike the TLR7 agonist, the structurally diverse STING agonists partially depleted B and NK cells and completely depleted CD14+ monocytes via induction of apoptosis. The TANK-binding kinase 1 inhibitor efficiently prevented interferon alpha (IFN alpha) secretion and cell depletion, suggesting their possible dependence on the cGAS-STING pathway activation. Finally, IFN alpha, tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta secretion and CD14+ monocyte apoptosis were primary responses to STING agonists, whereas IFN gamma was secreted secondarily. These findings bring new insights into the cGAS-STING pathway immunomodulation that is of future therapeutic importance.
Permanent Link: http://hdl.handle.net/11104/0330938