{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:14:25Z","timestamp":1779909265219,"version":"3.53.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Brucella abortus is a facultative intracellular bacterium that causes brucellosis, a prevalent zoonosis that leads to abortion and infertility in cattle, and undulant fever, debilitating arthritis, endocarditis, and meningitis in humans. Signaling pathways triggered by B. abortus involves stimulator of IFN genes (STING), which leads to production of type I IFNs. In this study, we evaluated the pathway linking the unfolded protein response (UPR) and the endoplasmic reticulum\u2013resident transmembrane molecule STING, during B. abortus infection. We demonstrated that B. abortus infection induces the expression of the UPR target gene BiP and XBP1 in murine macrophages through a STING-dependent pathway. Additionally, we also observed that STING activation was dependent on the bacterial second messenger cyclic dimeric GMP. Furthermore, the Brucella-induced UPR is crucial for induction of multiple molecules linked to type I IFN signaling pathway, such as IFN-\u03b2, IFN regulatory factor 1, and guanylate-binding proteins. Furthermore, IFN-\u03b2 is also important for the UPR induction during B. abortus infection. Indeed, IFN-\u03b2 shows a synergistic effect in inducing the IRE1 axis of the UPR. In addition, priming cells with IFN-\u03b2 favors B. abortus survival in macrophages. Moreover, Brucella-induced UPR facilitates bacterial replication in vitro and in vivo. Finally, these results suggest that B. abortus\u2013induced UPR is triggered by bacterial cyclic dimeric GMP, in a STING-dependent manner, and that this response supports bacterial replication. In summary, association of STING and IFN-\u03b2 signaling pathways with Brucella-induced UPR unravels a novel link between innate immunity and endoplasmic reticulum stress that is crucial for bacterial infection outcome.<\/jats:p>","DOI":"10.4049\/jimmunol.1801233","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T18:48:29Z","timestamp":1553107709000},"page":"2671-2681","source":"Crossref","is-referenced-by-count":54,"title":["<i>Brucella abortus<\/i> Cyclic Dinucleotides Trigger STING-Dependent Unfolded Protein Response That Favors Bacterial Replication"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-3592","authenticated-orcid":false,"given":"Erika S","family":"Guimar\u00e3es","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte 30270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco T\u00falio R","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte 30270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-3290","authenticated-orcid":false,"given":"Priscila C","family":"Campos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte 30270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-9334","authenticated-orcid":false,"given":"Daniel S","family":"Mansur","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina , Florianopolis, Santa Catarina 88040-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-4890","authenticated-orcid":false,"given":"Adara A","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina , Florianopolis, Santa Catarina 88040-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-0977","authenticated-orcid":false,"given":"Jerome","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Splitter","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen N","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4062-5577","authenticated-orcid":false,"given":"Sergio C","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte 30270-901 ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais, Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico, Minist\u00e9rio de Ci\u00eancia Tecnologia e Inova\u00e7\u00e3o , Salvador 40110-160 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2025030417561747100_r1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nature06246","article-title":"Recognition of microorganisms and activation of the immune response","volume":"449","author":"Medzhitov","year":"2007","journal-title":"Nature"},{"key":"2025030417561747100_r2","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.immuni.2013.05.004","article-title":"Immune sensing of DNA","volume":"38","author":"Paludan","year":"2013","journal-title":"Immunity"},{"key":"2025030417561747100_r3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature07317","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. 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