Characterization of STING agonist-induced monocyte cell death reveals combination of apoptosis, pyroptosis and caspase 8 activation

Abstract

The cyclic-GMP-AMP synthase - stimulator of interferon genes (cGAS-STING) pathway senses double-strandedDNA in cytoplasm, a signal of invading pathogens or cell damage. The activation of the cGAS-STING pathwayinduces secretion of proinflammatory cytokines by immune cells that in turn modulate antiviral and antitumoralresponses. Therefore, synthetic activators of the cGAS-STING pathway, such as STING agonists, are oftherapeutic interest.We have recently demonstrated that STING agonists not only trigger cytokine production in peripheral bloodmononuclear cells (PBMCs) but also induce cell death of monocytes. Here we investigated the mechanisms ofmonocyte death in terms of apoptosis, pyroptosis and necroptosis.