{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:09:35Z","timestamp":1793905775376,"version":"4.8.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303044\/2020-9"],"award-info":[{"award-number":["303044\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ #01945\/17 , Rede#00140-16"],"award-info":[{"award-number":["APQ #01945\/17 , Rede#00140-16"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI116453"],"award-info":[{"award-number":["AI116453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/15358-7"],"award-info":[{"award-number":["2022\/15358-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Endoplasmic reticulum (ER) stress plays a major role in several inflammatory disorders. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios.\n                    <jats:italic>Brucella abortus<\/jats:italic>\n                    , an intracellular pathogen, triggers the UPR\n                    <jats:italic>via<\/jats:italic>\n                    Stimulator of interferon genes (STING), an important regulator of macrophage metabolism during\n                    <jats:italic>B. abortus<\/jats:italic>\n                    infection. However, whether ER stress pathways underlie macrophage metabolic function during\n                    <jats:italic>B. abortus<\/jats:italic>\n                    infection remains to be elucidated. Here, we showed that the UPR sensor inositol-requiring enzyme 1\u03b1 (IRE1\u03b1) is as an important component regulating macrophage immunometabolic function. In\n                    <jats:italic>B. abortus<\/jats:italic>\n                    infection, IRE1\u03b1 supports the macrophage inflammatory profile, favoring M1-like macrophages. IRE1\u03b1 drives the macrophage metabolic reprogramming in infected macrophages, contributing to the reduced oxidative phosphorylation and increased glycolysis. This metabolic reprogramming is probably associated with the IRE1\u03b1-dependent expression and stabilization of hypoxia-inducible factor-1 alpha (HIF-1\u03b1), an important molecule involved in cell metabolism that sustains the inflammatory profile in\n                    <jats:italic>B. abortus<\/jats:italic>\n                    -infected macrophages. Accordingly, we demonstrated that IRE1\u03b1 favors the generation of mitochondrial reactive oxygen species (mROS) which has been described as an HIF-1\u03b1 stabilizing factor. Furthermore, in infected macrophages, IRE1\u03b1 drives the production of nitric oxide and the release of IL-1\u03b2. Collectively, these data unravel a key mechanism linking the UPR and the immunometabolic regulation of macrophages in\n                    <jats:italic>Brucella<\/jats:italic>\n                    infection and highlight IRE1\u03b1 as a central pathway regulating macrophage metabolic function during infectious diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.1063221","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:03:10Z","timestamp":1672704190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["The endoplasmic reticulum stress sensor IRE1\u03b1 modulates macrophage metabolic function during Brucella abortus infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Erika S.","family":"Guimar\u00e3es","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco T\u00falio R.","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo C. 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