The cGAS-STING/MITA pathway in innate antiviral immunity and beyond

Abstract

Upon binding double-stranded DNA (dsDNA), the cyclic GMP-AMP (cGAMP) synthase (cGAS) catalyzes the synthesis of 2′,3′-cGAMP, which subsequently binds to the endoplasmic reticulum (ER)-resident adaptor STING/MITA and triggers STING trafficking to the Golgi apparatus and recruits TANK-binding kinase 1 (TBK1) to induce type I interferons (IFNs) and inflammatory cytokines. Aberrant activation of this pathway drives severe autoinflammatory diseases, such as STING-associated vasculopathy with onset in infancy (SAVI) and Coatomer subunit alpha (COPA) syndrome. Furthermore, recent studies have revealed STING as a multifaceted signaling integrator that orchestrates non-canonical responses, such as autophagy, regulated cell death programs, cellular senescence, immunometabolism, and tumorigenesis and tumor metastasis. In this review, we aim to summarize the molecular regulation and pathophysiological significance of the cGAS-STING pathway and highlight its crucial role in innate antiviral immunity and other broader fields.