STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis

0556396 - ÚOCHB 2023 RIV US eng J - Článek v odborném periodiku
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
Grant CEP: GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963
Klíčová slova: STING * cGAS-STING pathway * apoptosis * monocytes * proinflammatory cytokines * interferons
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.3, rok: 2022
Způsob publikování: Omezený přístup
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.
Trvalý link: http://hdl.handle.net/11104/0330938