Paper

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

Sergio Costa Oliveira, Splitter, Gary A, Hu, Tony, Smith, Judith A, Gutman, Delia, Jin Wen Tan, Liu, Yiping, Eickhoff, Jens, Dahl, Richard, Khan, Mike, Guimaraes, Erika, Cai, Fengwei, Harms, Jerome S, Barber, Glen N

2020

Overview

Brucellosis, caused by Brucella bacteria species, remains the most prevalent zoonotic disease worldwide. Brucella 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 Brucella infection in vivo. However, early during infection, Brucella down-regulated STING mRNA and protein. Down-regulation occurred post-transcriptionally, required live bacteria, the Brucella type IV secretion system, and was independent of host IRE1-RNase activity. Rather, Brucella induced a STING-targeting microRNA, miR-24-2. Furthermore, STING downregulation was inhibited by miR-24 anti-miRs and in mirn23a locus-deficient macrophages. Failure to suppress STING expression in mirn23a-/- macrophages correlated with diminished Brucella 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, Brucella 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.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Bacteria / Brucella / Brucellosis / Chronic infection / Down-regulation / Gene regulation / Infections / Innate immunity / Interferon / Macrophages / Microbiology / miRNA / Post-transcription / Replication / Ribonuclease / Zoonoses