Document Type
Article
Publication Date
1-1-2026
Original Citation
Gupta S,
Matsunaga J,
Ratitong B,
Manion A,
Ismaeel S,
Valadares D,
West A,
Kerur N,
Stehlik C,
Dorfleutner A,
Dagvadorj J,
Coburn J,
Wolf A,
Morrissey M,
Cassel S,
Haake D,
Sutterwala F.
cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice. PLoS Pathog. 2026;22(1):e1013250.
Keywords
JMG, Animals, Nucleotidyltransferases, Leptospira interrogans, Interferon Type I, Leptospirosis, Mice, Membrane Proteins, Mice, Knockout, Humans, Kidney, Signal Transduction, Mice, Inbred C57BL, Immunity, Innate, Macrophages, Receptor, Interferon alpha-beta, STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
JAX Source
PLoS Pathog. 2026;22(1):e1013250.
ISSN
1553-7374
PMID
41499635
DOI
https://doi.org/10.1371/journal.ppat.1013250
Abstract
Leptospira interrogans is the major causative agent of leptospirosis. Humans, canines and agricultural animals are susceptible to Leptospira 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 Leptospira spp. remains poorly defined. We show that L. interrogans 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 in vivo suggesting that cGAS-STING-driven type I IFN is required for the host defense against L. interrogans. These findings demonstrate the significance of cGAS-STING- dependent type I IFN signaling in mammalian innate immune responses to L. interrogans.