{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:47:55Z","timestamp":1794242875079,"version":"4.9.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The innate immune system promptly detects and responds to invading pathogens, with a key role played by the recognition of bacterial-derived DNA through pattern recognition receptors. The Z-DNA binding protein 1 (ZBP1) functions as a DNA sensor inducing type I interferon (IFN) production, innate immune responses and also inflammatory cell death. ZBP1 interacts with cytosolic DNA via its DNA-binding domains, crucial for its activation.\n                    <jats:italic>Brucella abortus<\/jats:italic>\n                    is the etiologic agent of brucellosis in livestock and humans, leading to significant economic losses and public health impact. Despite other innate immune sensors that recognize\n                    <jats:italic>B. abortus<\/jats:italic>\n                    DNA, including Toll-like receptor 9 and the Stimulator of interferon genes (STING), here we evaluated the ZBP1 participation as a cytosolic receptor sensing\n                    <jats:italic>Brucella<\/jats:italic>\n                    infection. Using macrophages derived from ZBP1 knockout (KO) mice we demonstrated that ZBP1 partially contributes to\n                    <jats:italic>IFN-\u03b2<\/jats:italic>\n                    expression upon\n                    <jats:italic>B. abortus<\/jats:italic>\n                    infection or\n                    <jats:italic>Brucella<\/jats:italic>\n                    DNA transfection. The knockdown of STING by siRNA decreased the residual IFN-\u03b2 signal elicited by\n                    <jats:italic>B. abortus<\/jats:italic>\n                    infection, demonstrating the presence of a redundant cytosolic DNA-sensing mechanism driving type I IFN production. Furthermore, ZBP1 is involved in type I IFN signaling inducing\n                    <jats:italic>IRF-1<\/jats:italic>\n                    expression. Additionally, ZBP1 also contributes to Unfolded Protein Response (UPR) activation during infection. However, ZBP1 does not influence the production of proinflammatory mediators, inflammasome activation and it is dispensable to control bacterial infection in mice or replication in macrophages. This study highlights the complex interactions of\n                    <jats:italic>Brucella<\/jats:italic>\n                    components with innate immune receptors and identifies ZBP1 as a sensor for\n                    <jats:italic>B. abortus<\/jats:italic>\n                    DNA-induced IFN-\u03b2 response.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1511949","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T01:14:32Z","timestamp":1736385272000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["ZBP1 senses Brucella abortus DNA triggering type I interferon signaling pathway and unfolded protein response activation"],"prefix":"10.3389","volume":"15","author":[{"given":"Marco T\u00falio R.","family":"Gomes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika S.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio C.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nature04946","article-title":"Intracellular pattern recognition receptors in the host response","volume":"442","author":"Meylan","year":"2006","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161293498","article-title":"Human Tlr9 confers responsiveness to bacterial DNA via species-specific Cpg motif recognition","volume":"98","author":"Bauer","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature06013","article-title":"Dai (Dlm-1\/Zbp1) is a cytosolic DNA sensor and an activator of innate immune response","volume":"448","author":"Takaoka","year":"2007","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801295105","article-title":"Regulation of innate immune responses by Dai (Dlm-1\/Zbp1) and other DNA-sensing molecules","volume":"105","author":"Wang","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"ra20","DOI":"10.1126\/scisignal.2002521","article-title":"Sting specifies Irf3 phosphorylation by tbk1 in the cytosolic DNA signaling pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci Signaling"},{"key":"B6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cytogfr.2024.03.005","article-title":"Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death","volume":"77","author":"Song","year":"2024","journal-title":"Cytokine Growth factor Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810224","article-title":"Zbp1: A powerful innate immune sensor and double-edged sword in host immunity","volume":"23","author":"Hao","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013752","article-title":"The Zalpha2 domain of Zbp1 is a molecular switch regulating influenza-induced panoptosis and perinatal lethality during development","volume":"295","author":"Kesavardhana","year":"2020","journal-title":"J Biol Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015924","article-title":"Zbp1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (Panoptosis)","volume":"295","author":"Banoth","year":"2020","journal-title":"J Biol Chem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.01.016","article-title":"Dai\/Zbp1\/Dlm-1 complexes with Rip3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vira","volume":"11","author":"Upton","year":"2012","journal-title":"Cell Host Microbe"},{"key":"B11","doi-asserted-by":"publisher","first-page":"aag2045","DOI":"10.1126\/sciimmunol.aag2045","article-title":"Zbp1\/Dai is an innate sensor of influenza virus triggering the Nlrp3 inflammasome and programmed cell death pathways","volume":"1","author":"Kuriakose","year":"2016","journal-title":"Sci Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03875-8","article-title":"Aim2 forms a complex with pyrin and Zbp1 to drive panoptosis and host defence","volume":"597","author":"Lee","year":"2021","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110291","article-title":"Cisatracurium besylate rescues mycobacterium tuberculosis-infected macrophages from necroptosis and enhances the bactericidal effect of isoniazid","volume":"120","author":"Wen","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050570","article-title":"Brucellosis","volume":"352","author":"Pappas","year":"2005","journal-title":"New Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(07)70286-4","article-title":"Human brucellosis","volume":"7","author":"Franco","year":"2007","journal-title":"Lancet Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1586\/erv.11.110","article-title":"Confronting the barriers to develop novel vaccines against brucellosis","volume":"10","author":"Oliveira","year":"2011","journal-title":"Expert Rev Vaccines"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39497.431528.80","article-title":"Treatment of brucellosis","volume":"336","author":"Pappas","year":"2008","journal-title":"BMJ"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00130","article-title":"The role of innate immune signals in immunity to brucella abortus","volume":"2","author":"Gomes","year":"2012","journal-title":"Front Cell infection Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A0815-346R","article-title":"Tlr9 is required for mapk\/nf-kappab activation but does not cooperate with Tlr2 or Tlr6 to induce host resistance to brucella abortus","volume":"99","author":"Gomes","year":"2016","journal-title":"J leukocyte Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202817","article-title":"Critical role of asc inflammasomes and bacterial type iv secretion system in caspase-1 activation and host innate resistance to brucella abortus infection","volume":"190","author":"Gomes","year":"2013","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700725","article-title":"Brucella abortus triggers a cgas-independent sting pathway to induce host protection that involves guanylate-binding proteins and inflammasome activation","volume":"200","author":"Costa Franco","year":"2018","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801233","article-title":"Brucella abortus cyclic dinucleotides trigger sting-dependent unfolded protein response that favors bacterial replication","volume":"202","author":"Guimaraes","year":"2019","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476","article-title":"Sting regulates intracellular DNA-mediated, type I interferon-dependent innate immunity","volume":"461","author":"Ishikawa","year":"2009","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009597","article-title":"Sting regulates metabolic reprogramming in macrophages via Hif-1alpha during brucella infection","volume":"17","author":"Gomes","year":"2021","journal-title":"PLoS Pathog"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201848016","article-title":"Brucella abortus nitric oxide metabolite regulates inflammasome activation and Il-1beta secretion in murine macrophages","volume":"49","author":"Campos","year":"2019","journal-title":"Eur J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009220","article-title":"Interferon regulatory factor 1 (Irf1) and anti-pathogen innate immune responses","volume":"17","author":"Feng","year":"2021","journal-title":"PLoS Pathog"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01444-16","article-title":"Interferon regulatory factor 1 and type I interferon cooperate to control acute gammaherpesvirus infection","volume":"91","author":"Mboko","year":"2017","journal-title":"J Virol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41467-020-20357-z","article-title":"Zbp1 promotes lps-induced cell death and Il-1beta release via rhim-mediated interactions with ripk1","volume":"12","author":"Muendlein","year":"2021","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/imr.12909","article-title":"The regulation of the Zbp1-Nlrp3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (Panoptosis)","volume":"297","author":"Zheng","year":"2020","journal-title":"Immunol Rev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.09.014","article-title":"Dai senses influenza a virus genomic rna and activates Ripk3-dependent cell death","volume":"20","author":"Thapa","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007519","article-title":"Guanylate-binding protein 5 licenses caspase-11 for gasdermin-D mediated host resistance to Brucella abortus infection","volume":"14","author":"Cerqueira","year":"2018","journal-title":"PLoS Pathog"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023135","article-title":"Myd88 and sting signaling pathways are required for Irf3-mediated Ifn-beta induction in response to brucella abortus infection","volume":"6","author":"de Almeida","year":"2011","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3109\/08830185.2010.529976","article-title":"Pathogen recognition by the innate immune system","volume":"30","author":"Kumar","year":"2011","journal-title":"Int Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.08.010","article-title":"Brucella abortus DNA is a major bacterial agonist to activate the host innate immune system","volume":"16","author":"Campos","year":"2014","journal-title":"Microbes infection"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: from stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003785","article-title":"Brucella induces an unfolded protein response via tcpb that supports intracellular replication in macrophages","volume":"9","author":"Smith","year":"2013","journal-title":"PLoS Pathog"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000110","article-title":"Rnai screen of endoplasmic reticulum-associated host factors reveals a role for ire1alpha in supporting brucella replication","volume":"4","author":"Qin","year":"2008","journal-title":"PLoS Pathog"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004747","article-title":"Yip1a, a novel host factor for the activation of the Ire1 pathway of the unfolded protein response during brucella infection","volume":"11","author":"Taguchi","year":"2015","journal-title":"PLoS Pathog"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9121040","article-title":"Lack of interleukin-6 affects Ifn-gamma and Tnf-alpha production and early in vivo control of Brucella abortus infection","volume":"9","author":"Guimaraes","year":"2020","journal-title":"Pathogens"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6427","article-title":"Receptor-interacting protein homotypic interaction motif-dependent control of Nf-Kappa B activation via the DNA-dependent activator of Ifn regulatory factors","volume":"181","author":"Kaiser","year":"2008","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1342684","article-title":"Brucella infection and toll-like receptors","volume":"14","author":"Yu","year":"2024","journal-title":"Front Cell infection Microbiol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1511949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T01:14:34Z","timestamp":1736385274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1511949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2024.1511949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1511949","relation":{"has-part":[{"id-type":"doi","id":"https:\/\/doi.org\/10.3389\/fimmu.2024.1511949.s001","asserted-by":"subject"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]},"article-number":"1511949"}}