cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice

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.

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Publication Details

Journal
PLoS Pathogens
Published
2026-01-07
DOI
https://doi.org/10.1371/journal.ppat.1013250
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
0.00
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article

cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice

Jargalsaikhan Dagvadorj, James Matsunaga, Jenifer Coburn, Fayyaz S. Sutterwala et al.
PLoS Pathogens
interferon and immune responses
article

cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice

Jargalsaikhan Dagvadorj, James Matsunaga, Jenifer Coburn, Fayyaz S. Sutterwala, Christian Stehlik, Andrea J. Wolf, Sana Ismaeel, Andrea Dorfleutner, David A. Haake, Nagaraj Kerur, Bridget Ratitong, Suzanne L. Cassel, Diogo G. Valadares, Suman Gupta, A. Phillip West, Meghan A. Morrissey, Andrew Manion
article en

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.

PLoS PathogensVol. 22(1)
Cedars-Sinai Medical Center (US), University of California, Santa Barbara (US), University of California, Los Angeles (US), Medical College of Wisconsin (US), The Ohio State University Wexner Medical Center (US), Lung Institute (US), Jackson Laboratory (US), Cedars-Sinai Smidt Heart Institute (US), VA Greater Los Angeles Healthcare System (US)
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