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Here, we reveal a distinct mechanism by which stimulator of interferon genes (STING), a cytosolic sensor that regulates innate immune responses, contributes to an inflammatory M1-like macrophage profile upon\n                    <jats:italic>Brucella abortus<\/jats:italic>\n                    infection. This metabolic reprogramming is induced by STING-dependent stabilization of hypoxia-inducible factor-1 alpha (HIF-1\u03b1), a global regulator of cellular metabolism and innate immune cell functions. HIF-1\u03b1 stabilization reduces oxidative phosphorylation and increases glycolysis during infection with\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>abortus<\/jats:italic>\n                    and, likewise, enhances nitric oxide production, inflammasome activation and IL-1\u03b2 release in infected macrophages. Furthermore, the induction of this inflammatory profile participates in the control of bacterial replication since absence of HIF-1\u03b1 renders mice more susceptible to\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>abortus<\/jats:italic>\n                    infection. Mechanistically, activation of STING by\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>abortus<\/jats:italic>\n                    infection drives the production of mitochondrial reactive oxygen species (mROS) that ultimately influences HIF-1\u03b1 stabilization. Moreover, STING increases the intracellular succinate concentration in infected macrophages, and succinate pretreatment induces HIF-1\u03b1 stabilization and IL-1\u03b2 release independently of its cognate receptor GPR91. Collectively, these data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>abortus<\/jats:italic>\n                    infection that is orchestrated by STING via HIF-1\u03b1 pathway and highlight the metabolic reprogramming of macrophages as a potential treatment strategy for bacterial infections.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009597","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T13:47:45Z","timestamp":1621000065000},"page":"e1009597","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":115,"title":["STING regulates metabolic reprogramming in macrophages via HIF-1\u03b1 during Brucella infection"],"prefix":"10.1371","volume":"17","author":[{"given":"Marco Tulio 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6885-3438","authenticated-orcid":true,"given":"Fabio V.","family":"Marinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8143-5756","authenticated-orcid":true,"given":"Eric R. G. R.","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen N.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-786X","authenticated-orcid":true,"given":"Pedro M. 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