Phagosome-mediated activation of STING during diverse bacterial infections

Central to health and disease are innate immune receptors that bind bacterial molecules to initiate inflammation and host defense. Beyond pathogens and their membrane disruptive activities, mechanisms enabling bacterial molecules to access innate immune receptors in the cytoplasm are unknown. Here, we describe the cytoplasmic cyclic dinucleotide (CDN)-binding protein STING as a common bacterial sensor. Irrespective of virulence and after bacteriolysis in phagolysosomes, CDNs produced during infections with evolutionarily diverse bacteria activate STING. Of the several known CDN transporters, two supported bacteria-induced STING activation. We propose a connection between phagocytosis and STING that ensures host-bacteria interactions result in STING activation.