{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:32Z","timestamp":1787022212516,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013250","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI168148"],"award-info":[{"award-number":["P01 AI168148"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI175101"],"award-info":[{"award-number":["R01 AI175101"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI177233"],"award-info":[{"award-number":["R01 AI177233"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM146935"],"award-info":[{"award-number":["R35 GM146935"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRR-85-25"],"award-info":[{"award-number":["DRR-85-25"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Leptospira interrogans<\/jats:italic>\n                    is the major causative agent of leptospirosis. Humans, canines and agricultural animals are susceptible to\n                    <jats:italic>Leptospira<\/jats:italic>\n                    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\n                    <jats:italic>Leptospira<\/jats:italic>\n                    spp. remains poorly defined. We show that\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    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 IFN\u03b1\/\u03b2 receptor subunit 1 (IFNAR1) or STING had higher bacterial burdens and increased renal colonization following infection\n                    <jats:italic>in vivo<\/jats:italic>\n                    suggesting that cGAS-STING-driven type I IFN is required for the host defense against\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    . These findings demonstrate the significance of cGAS-STING- dependent type I IFN signaling in mammalian innate immune responses to\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013250","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T19:36:29Z","timestamp":1767814589000},"page":"e1013250","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["cGAS-STING dependent type I IFN reduces Leptospira interrogans renal colonization in mice"],"prefix":"10.1371","volume":"22","author":[{"given":"Suman","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Matsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Ratitong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Manion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Ismaeel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo G.","family":"Valadares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Phillip","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaraj","family":"Kerur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Stehlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Dorfleutner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jargalsaikhan","family":"Dagvadorj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan A.","family":"Morrissey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L.","family":"Cassel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Haake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7338-3095","authenticated-orcid":true,"given":"Fayyaz S.","family":"Sutterwala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"issue":"7","key":"ppat.1013250.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012161","article-title":"Evolutionary insights into the emergence of virulent Leptospira spirochetes","volume":"20","author":"A Giraud-Gatineau","year":"2024","journal-title":"PLoS Pathog"},{"key":"ppat.1013250.ref002","first-page":"99","article-title":"Animal leptospirosis","volume":"387","author":"WA Ellis","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"issue":"9","key":"ppat.1013250.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global Morbidity and Mortality of Leptospirosis: A Systematic Review","volume":"9","author":"F Costa","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"ppat.1013250.ref004","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrmicro2208","article-title":"Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen","volume":"7","author":"AI Ko","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"ppat.1013250.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003359","article-title":"Live imaging of bioluminescent leptospira interrogans in mice reveals renal colonization as a stealth escape from the blood defenses and antibiotics","volume":"8","author":"G Ratet","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1013250.ref006","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"DA Haake","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"ppat.1013250.ref007","doi-asserted-by":"crossref","first-page":"571816","DOI":"10.3389\/fimmu.2020.571816","article-title":"Phagocyte Escape of Leptospira: The Role of TLRs and NLRs","volume":"11","author":"I Santecchia","year":"2020","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1013250.ref008","first-page":"463","article-title":"The role of macrophages in the protection of mice against leptospirosis: in vitro and in vivo studies","volume":"14","author":"V Tu","year":"1982","journal-title":"Pathology"},{"issue":"1","key":"ppat.1013250.ref009","first-page":"65","article-title":"Phagocytosis as a defense mechanism against infection with leptospiras","volume":"261","author":"E Isogai","year":"1986","journal-title":"Zentralbl Bakteriol Mikrobiol Hyg A"},{"issue":"5","key":"ppat.1013250.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007811","article-title":"Innate immune memory through TLR2 and NOD2 contributes to the control of Leptospira interrogans infection","volume":"15","author":"I Santecchia","year":"2019","journal-title":"PLoS Pathog"},{"key":"ppat.1013250.ref011","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fcimb.2018.00384","article-title":"Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis","volume":"8","author":"MF Ferrer","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"ppat.1013250.ref012","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1128\/iai.65.2.729-738.1997","article-title":"Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic Leptospira interrogans are correlated with virulence","volume":"65","author":"F Merien","year":"1997","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1013250.ref013","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1111\/j.1462-5822.2011.01660.x","article-title":"Characteristic features of intracellular pathogenic Leptospira in infected murine macrophages","volume":"13","author":"C Toma","year":"2011","journal-title":"Cell Microbiol"},{"issue":"6","key":"ppat.1013250.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000463","article-title":"Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues","volume":"3","author":"JM Davis","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1013250.ref015","doi-asserted-by":"crossref","first-page":"936931","DOI":"10.3389\/fcimb.2022.936931","article-title":"Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication","volume":"12","author":"I Santecchia","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"ppat.1013250.ref016","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","article-title":"The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling","volume":"54","author":"X Cai","year":"2014","journal-title":"Mol Cell"},{"issue":"6","key":"ppat.1013250.ref017","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.chom.2015.05.004","article-title":"The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy","volume":"17","author":"RO Watson","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"6148","key":"ppat.1013250.ref018","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1240933","article-title":"Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses","volume":"341","author":"D Gao","year":"2013","journal-title":"Science"},{"issue":"15","key":"ppat.1013250.ref019","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.15252\/embj.201488029","article-title":"Listeria monocytogenes induces IFN\u03b2 expression through an IFI16-, cGAS- and STING-dependent pathway","volume":"33","author":"K Hansen","year":"2014","journal-title":"EMBO J"},{"issue":"1","key":"ppat.1013250.ref020","doi-asserted-by":"crossref","first-page":"101928","DOI":"10.1016\/j.isci.2020.101928","article-title":"Identification of cGAS as an innate immune sensor of extracellular bacterium Pseudomonas aeruginosa","volume":"24","author":"C-M Zhou","year":"2020","journal-title":"iScience"},{"issue":"17","key":"ppat.1013250.ref021","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1016\/j.jmb.2016.04.030","article-title":"For Better or Worse: Cytosolic DNA Sensing during Intracellular Bacterial Infection Induces Potent Innate Immune Responses","volume":"428","author":"KL Patrick","year":"2016","journal-title":"J Mol Biol"},{"issue":"5","key":"ppat.1013250.ref022","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"LC Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"issue":"11","key":"ppat.1013250.ref023","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.4049\/jimmunol.2200354","article-title":"Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway","volume":"210","author":"LC Farris","year":"2023","journal-title":"J Immunol"},{"issue":"7","key":"ppat.1013250.ref024","doi-asserted-by":"crossref","first-page":"104866","DOI":"10.1016\/j.jbc.2023.104866","article-title":"Regulation of cGAS and STING signaling during inflammation and infection","volume":"299","author":"SD Chauvin","year":"2023","journal-title":"J Biol Chem"},{"issue":"7747","key":"ppat.1013250.ref025","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41586-019-0953-5","article-title":"Bacterial cGAS-like enzymes synthesize diverse nucleotide signals","volume":"567","author":"AT Whiteley","year":"2019","journal-title":"Nature"},{"issue":"7780","key":"ppat.1013250.ref026","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41586-019-1605-5","article-title":"Cyclic GMP-AMP signalling protects bacteria against viral infection","volume":"574","author":"D Cohen","year":"2019","journal-title":"Nature"},{"issue":"4","key":"ppat.1013250.ref027","article-title":"cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity","volume":"20","author":"H Liu","year":"2019","journal-title":"EMBO Rep"},{"issue":"1","key":"ppat.1013250.ref028","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41522-020-0134-1","article-title":"The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production","volume":"6","author":"R Thibeaux","year":"2020","journal-title":"NPJ Biofilms Microbiomes"},{"issue":"15","key":"ppat.1013250.ref029","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.jmb.2017.06.002","article-title":"Structural and Enzymatic Characterization of a cAMP-Dependent Diguanylate Cyclase from Pathogenic Leptospira Species","volume":"429","author":"FN da Costa Vasconcelos","year":"2017","journal-title":"J Mol Biol"},{"issue":"4","key":"ppat.1013250.ref030","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.4049\/jimmunol.0900506","article-title":"TLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans","volume":"183","author":"C Chassin","year":"2009","journal-title":"J Immunol"},{"issue":"6","key":"ppat.1013250.ref031","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.4049\/jimmunol.1101987","article-title":"Downregulation of the Na\/K-ATPase pump by leptospiral glycolipoprotein activates the NLRP3 inflammasome","volume":"188","author":"S Lacroix-Lamand\u00e9","year":"2012","journal-title":"J Immunol"},{"issue":"6227","key":"ppat.1013250.ref032","article-title":"Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation","volume":"347","author":"S Liu","year":"2015","journal-title":"Science"},{"issue":"2","key":"ppat.1013250.ref033","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1083\/jcb.200307080","article-title":"The uniformity of phagosome maturation in macrophages","volume":"164","author":"RM Henry","year":"2004","journal-title":"J Cell Biol"},{"issue":"5","key":"ppat.1013250.ref034","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/0092-8674(92)90306-W","article-title":"The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway","volume":"70","author":"C Bucci","year":"1992","journal-title":"Cell"},{"key":"ppat.1013250.ref035","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1083\/jcb.132.1.49","article-title":"Phagosome-lysosome fusion is a calcium-independent event in macrophages","volume":"132","author":"S Zimmerli","year":"1996","journal-title":"J Cell Biol"},{"key":"ppat.1013250.ref036","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1242\/jcs.113.19.3531","article-title":"Rab5 regulates the kiss and run fusion between phagosomes and endosomes and the acquisition of phagosome leishmanicidal properties in RAW 264.7 macrophages","author":"S Duclos","year":"2000","journal-title":"J Cell Sci"},{"issue":"21","key":"ppat.1013250.ref037","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1073\/pnas.85.21.7972","article-title":"Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells","volume":"85","author":"EJ Bowman","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ppat.1013250.ref038","doi-asserted-by":"crossref","first-page":"110","DOI":"10.7164\/antibiotics.37.110","article-title":"Metabolic products of microorganisms. 224. Bafilomycins, a new group of macrolide antibiotics. Production, isolation, chemical structure and biological activity","volume":"37","author":"G Werner","year":"1984","journal-title":"J Antibiot (Tokyo)"},{"issue":"26","key":"ppat.1013250.ref039","doi-asserted-by":"crossref","first-page":"17707","DOI":"10.1016\/S0021-9258(19)47429-2","article-title":"Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells","volume":"266","author":"T Yoshimori","year":"1991","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"ppat.1013250.ref040","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/00004872-198406000-00010","article-title":"Evidence for a putatively new angiotensin II-generating enzyme in the vascular wall","volume":"2","author":"H Okunishi","year":"1984","journal-title":"J Hypertens"},{"issue":"3","key":"ppat.1013250.ref041","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.pharmthera.2006.05.008","article-title":"Pathological roles of angiotensin II produced by mast cell chymase and the effects of chymase inhibition in animal models","volume":"112","author":"M Miyazaki","year":"2006","journal-title":"Pharmacol Ther"},{"issue":"10","key":"ppat.1013250.ref042","doi-asserted-by":"crossref","DOI":"10.1128\/aem.01204-23","article-title":"Concurrent colonization of rodent kidneys with multiple species and serogroups of pathogenic Leptospira","volume":"89","author":"C Hamond","year":"2023","journal-title":"Appl Environ Microbiol"},{"key":"ppat.1013250.ref043","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.3389\/fmicb.2020.02005","article-title":"Investigating the Immunological and Biological Equilibrium of Reservoir Hosts and Pathogenic Leptospira: Balancing the Solution to an Acute Problem?","volume":"11","author":"EJ Putz","year":"2020","journal-title":"Front Microbiol"},{"issue":"5","key":"ppat.1013250.ref044","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrmicro.2017.5","article-title":"Virulence of the zoonotic agent of leptospirosis: still terra incognita?","volume":"15","author":"M Picardeau","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"10","key":"ppat.1013250.ref045","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing","volume":"17","author":"Q Chen","year":"2016","journal-title":"Nat Immunol"},{"issue":"3","key":"ppat.1013250.ref046","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.celrep.2014.01.003","article-title":"The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop","volume":"6","author":"X Zhang","year":"2014","journal-title":"Cell Rep"},{"issue":"6","key":"ppat.1013250.ref047","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.immuni.2013.10.019","article-title":"Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization","volume":"39","author":"X Li","year":"2013","journal-title":"Immunity"},{"issue":"6121","key":"ppat.1013250.ref048","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1126\/science.1229963","article-title":"Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA","volume":"339","author":"J Wu","year":"2013","journal-title":"Science"},{"issue":"7213","key":"ppat.1013250.ref049","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature07317","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling","volume":"455","author":"H Ishikawa","year":"2008","journal-title":"Nature"},{"issue":"4","key":"ppat.1013250.ref050","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.immuni.2008.09.003","article-title":"The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation","volume":"29","author":"B Zhong","year":"2008","journal-title":"Immunity"},{"issue":"5","key":"ppat.1013250.ref051","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"KA Fitzgerald","year":"2003","journal-title":"Nat Immunol"},{"issue":"214","key":"ppat.1013250.ref052","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2002521","article-title":"STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway","volume":"5","author":"Y Tanaka","year":"2012","journal-title":"Sci Signal"},{"issue":"5622","key":"ppat.1013250.ref053","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1126\/science.1081315","article-title":"Triggering the interferon antiviral response through an IKK-related pathway","volume":"300","author":"S Sharma","year":"2003","journal-title":"Science"},{"issue":"3","key":"ppat.1013250.ref054","article-title":"Salmonella Induces the cGAS-STING-Dependent Type I Interferon Response in Murine Macrophages by Triggering mtDNA Release","volume":"13","author":"L Xu","year":"2022","journal-title":"mBio"},{"issue":"5","key":"ppat.1013250.ref055","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.immuni.2013.05.007","article-title":"Cytosolic sensing of viruses","volume":"38","author":"D Goubau","year":"2013","journal-title":"Immunity"},{"issue":"5","key":"ppat.1013250.ref056","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","article-title":"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3","volume":"122","author":"RB Seth","year":"2005","journal-title":"Cell"},{"issue":"7086","key":"ppat.1013250.ref057","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature04641","article-title":"IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9","volume":"440","author":"K Hoshino","year":"2006","journal-title":"Nature"},{"issue":"6","key":"ppat.1013250.ref058","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.20042372","article-title":"Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction","volume":"201","author":"S Uematsu","year":"2005","journal-title":"J Exp Med"},{"issue":"12","key":"ppat.1013250.ref059","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1084\/jem.20040528","article-title":"Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection","volume":"199","author":"AK Perry","year":"2004","journal-title":"J Exp Med"},{"issue":"12","key":"ppat.1013250.ref060","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1084\/jem.20040520","article-title":"The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection","volume":"199","author":"H Hemmi","year":"2004","journal-title":"J Exp Med"},{"issue":"10","key":"ppat.1013250.ref061","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/ni1243","article-title":"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction","volume":"6","author":"T Kawai","year":"2005","journal-title":"Nat Immunol"},{"issue":"9","key":"ppat.1013250.ref062","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nri1900","article-title":"IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors","volume":"6","author":"K Honda","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"ppat.1013250.ref063","doi-asserted-by":"crossref","first-page":"105571","DOI":"10.1016\/j.ebiom.2025.105571","article-title":"Myocarditis and neutrophil-mediated vascular leakage but not cytokine storm associated with fatal murine leptospirosis","volume":"112","author":"S Papadopoulos","year":"2025","journal-title":"EBioMedicine"},{"issue":"2","key":"ppat.1013250.ref064","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1128\/IAI.00999-10","article-title":"The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides","volume":"79","author":"J-D Sauer","year":"2011","journal-title":"Infect Immun"},{"issue":"7485","key":"ppat.1013250.ref065","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nature12862","article-title":"Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity","volume":"505","author":"JW Schoggins","year":"2014","journal-title":"Nature"},{"issue":"11","key":"ppat.1013250.ref066","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.4049\/jimmunol.1501553","article-title":"Type I IFNs Act upon Hematopoietic Progenitors To Protect and Maintain Hematopoiesis during Pneumocystis Lung Infection in Mice","volume":"195","author":"JR Prigge","year":"2015","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1013250.ref067","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.1038\/s41598-020-66526-4","article-title":"Isolation and propagation of leptospires at 37\u2009\u00b0C directly from the mammalian host","volume":"10","author":"RL Hornsby","year":"2020","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1013250.ref068","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1083\/jcb.201610060","article-title":"Localization of mTORC2 activity inside cells","volume":"216","author":"M Ebner","year":"2017","journal-title":"J Cell Biol"},{"key":"ppat.1013250.ref069","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36688","article-title":"Chimeric antigen receptors that trigger phagocytosis","volume":"7","author":"MA Morrissey","year":"2018","journal-title":"Elife"},{"issue":"1","key":"ppat.1013250.ref070","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1038\/s41467-021-26240-9","article-title":"A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling","volume":"12","author":"D Banerjee","year":"2021","journal-title":"Nat Commun"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013250","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T18:50:36Z","timestamp":1768243836000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013250"}},"subtitle":[],"editor":[{"given":"Dana J.","family":"Philpott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013250","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}