STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00556396" target="_blank" >RIV/61388963:_____/22:00556396 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/22:10451128

Výsledek na webu

<a href="https://doi.org/10.1021/acsinfecdis.1c00554" target="_blank" >https://doi.org/10.1021/acsinfecdis.1c00554</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsinfecdis.1c00554" target="_blank" >10.1021/acsinfecdis.1c00554</a>

Jazyk výsledku

angličtina

Název v původním jazyce

STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

ACS Infectious Diseases

ISSN

2373-8227

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

463-471

Kód UT WoS článku

000772168200009

EID výsledku v databázi Scopus

2-s2.0-85125037291