cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice. PLoS Pathog 2026 Jan;22(1):e1013250
Date
01/07/2026Pubmed ID
41499635Pubmed Central ID
PMC12795460DOI
10.1371/journal.ppat.1013250Scopus ID
2-s2.0-105027301367 (requires institutional sign-in at Scopus site) 1 CitationAbstract
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.
Author List
Gupta S, Matsunaga J, Ratitong B, Manion A, Ismaeel S, Valadares DG, West AP, Kerur N, Stehlik C, Dorfleutner A, Dagvadorj J, Coburn J, Wolf AJ, Morrissey MA, Cassel SL, Haake DA, Sutterwala FSAuthor
Jenifer Coburn PhD, MA Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsHumans
Immunity, Innate
Interferon Type I
Kidney
Leptospira interrogans
Leptospirosis
Macrophages
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Nucleotidyltransferases
Receptor, Interferon alpha-beta
Signal Transduction
