Brucella abortus Cyclic Dinucleotides Trigger STING-Dependent Unfolded Protein Response That Favors Bacterial...

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Brucella abortus causes brucellosis, a zoonotic disease affecting livestock and humans.
• B. abortus infection activates the stimulator of IFN genes (STING) pathway, leading to type I IFN production.

Purpose of the Study:

• To investigate the link between the unfolded protein response (UPR) and STING during B. abortus infection.
• To elucidate the role of UPR and STING in bacterial replication and host immune response.

Main Methods:

• Murine macrophages were infected with B. abortus.
• Expression of UPR genes (BiP, XBP1) and IFN-β was analyzed.
• STING-dependent pathways and cyclic dimeric GMP involvement were assessed.
• Bacterial replication in vitro and in vivo was evaluated.

Main Results:

• B. abortus infection induced UPR genes (BiP, XBP1) via a STING-dependent pathway.
• STING activation required bacterial cyclic dimeric GMP.
• Brucella-induced UPR promoted type I IFN signaling molecules (IFN-β, IRF1, GBP).
• IFN-β synergistically induced the UPR and favored B. abortus survival and replication.

Conclusions:

• B. abortus-induced UPR is triggered by cyclic dimeric GMP in a STING-dependent manner.
• The UPR supports bacterial replication in vitro and in vivo.
• A novel link exists between STING, IFN-β signaling, UPR, and B. abortus infection outcome.