Drosophila melanogaster Sting mediates Coxiella burnetii infection by reducing accumulation of reactive oxygen species

The Gram-negative bacterium is the causative agent of query fever in humans and coxiellosis in livestock. infects a variety of cell types, tissues, and animal species including mammals and arthropods, but there is much left to be understood about the molecular mechanisms at play during infection in distinct species. Human stimulator of interferon genes (STING) induces an innate immune response through the induction of type I interferons (IFNs), and IFN promotes or suppresses replication, depending on tissue type. contains a functional STING ortholog (Sting) which activates NF-κB signaling and autophagy. Here, we sought to address the role of Sting during infection to uncover how Sting regulates infection in flies. We show that Sting-null flies exhibit higher mortality and reduced induction of antimicrobial peptides following infection compared to control flies. Additionally Sting-null flies induce lower levels of oxidative stress genes during infection, but the provision of N-acetyl-cysteine (NAC) in food rescues Sting-null host survival. Lastly, we find that reactive oxygen species levels during infection are higher in S2 cells knocked down for Sting compared to control cells. Our results show that at the host level, NAC provides protection against infection in the absence of Sting, thus establishing a role for Sting in protection against oxidative stress during infection.