Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.

Bacterial cyclic dinucleotides, including pyrimidine-based ones, escape the phagosome and activate STING, triggering innate immune responses across diverse bacteria.

• Why it matters: Understanding how the immune system detects bacteria beyond Toll-like receptors is crucial for developing new therapies for infections and inflammatory diseases, such as inflammatory bowel disease.
• What they did: The study examined the role of STING in sensing bacterial CDNs, revealing their presence in tissues, their activation after phagolysosomal bacteriolysis, and their increased levels in patients with inflammatory bowel disease, using murine models and human biopsies.
• The result: Bacterial CDNs activate STING through distinct binding modes, promoting immune responses and anti-tumor immunity, highlighting a conserved mechanism linking phagocytosis to cytoplasmic immune sensing.