Brucella suppress innate immunity by down-regulating STING expression in macrophages

Brucellosis, caused by bacteria species, remains the most prevalent zoonotic disease worldwide. establish chronic infections within host macrophages despite triggering cytosolic innate immune sensors, including Stimulator of Interferon Genes (STING), which potentially limit infection. In this study, STING was required for control of chronic infection . However, early during infection, down-regulated STING mRNA and protein. Down-regulation occurred post-transcriptionally, required live bacteria, the type IV secretion system, and was independent of host IRE1-RNase activity. Rather, induced a STING-targeting microRNA, miR-24-2. Furthermore, STING downregulation was inhibited by miR-24 anti-miRs and in locus-deficient macrophages. Failure to suppress STING expression in macrophages correlated with diminished replication, and was rescued by exogenous miR-24. Anti-miR-24 potently suppressed replication in wild type, but much less in STING macrophages, suggesting most of the impact of miR-24 induction on replication occurred via STING suppression. In summary, sabotages innate immunity by miR-24-dependent suppression of STING expression; post-STING activation “damage control” via targeted STING destruction may enable establishment of chronic infection.