STING agonists induce monocyte depletion with characteristics of multiple regulated cell deaths

Abstract

Double-stranded DNA and cyclic dinucleotides activate the cyclic-GMP-AMP synthase - stimulator of interferon genes (cGAS-STING) pathway, which leads to the production of type I interferons (IFNs) and proinflammatory cytokines by immune cells. These compounds further mediate numerous regulatory immune processes with antiviral or antitumoral properties. Therefore, activators of the cGAS-STING pathway are being investigated for their therapeutic potential.To better understand the immune orchestration induced by STING agonists, we investigated their effect on peripheral blood mononuclear cells (PBMCs), a physiologically relevant complex of immune populations. We demonstrated that STING agonists induce the secretion of a broad portfolio of proinflammatory cytokines. However, treatment with STING agonist is also associated with robust monocyte depletion.