cGAS-STING dependent type I IFN protects against renal colonization in mice.

is the major causative agent of leptospirosis. Humans, canines and livestock animals are susceptible to species and can develop fulminant disease. Rodents serve as reservoir hosts in which the bacteria colonize the renal tubules and are excreted in the urine. The host immune response to spp. remains poorly defined. We show that induces a robust type I interferon (IFN) response in human and murine macrophages that is dependent on the cytosolic dsDNA sensor Cyclic GMP-AMP Synthase (cGAS) and the Stimulator of IFN Genes (STING) signaling pathway. Further, we show that mice deficient in the IFNα/β receptor subunit 1 (IFNAR1) or STING had higher bacterial burdens and increased renal colonization following infection suggesting that cGAS-STING-driven type I IFN is required for the host defense against . These findings demonstrate the significance of cGAS-STING- dependent type I IFN signaling in mammalian innate immune responses to .