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-stranded DNA in cytoplasm, a signal of invading pathogens or cell damage. The activation of the cGAS-STING pathway induces secretion of proinflammatory cytokines by immune cells that in turn modulate antiviral and antitumoral responses. Therefore, synthetic activators of the cGAS-STING pathway, such as STING agonists, are of therapeutic interest.We have recently demonstrated that STING agonists not only trigger cytokine production in peripheral blood mononuclear cells (PBMCs) but also induce cell death of monocytes. Here we investigated the mechanisms of monocyte death in terms of apoptosis, pyroptosis and necroptosis.