{"doi":"10.1371/journal.ppat.1009597","title":"STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection","abstract":"Macrophages metabolic reprogramming in response to microbial insults is a major determinant of pathogen growth or containment. 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 Brucella abortus infection. This metabolic reprogramming is induced by STING-dependent stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), a global regulator of cellular metabolism and innate immune cell functions. HIF-1α stabilization reduces oxidative phosphorylation and increases glycolysis during infection with B. abortus and, likewise, enhances nitric oxide production, inflammasome activation and IL-1β release in infected macrophages. Furthermore, the induction of this inflammatory profile participates in the control of bacterial replication since absence of HIF-1α renders mice more susceptible to B. abortus infection. Mechanistically, activation of STING by B. abortus infection drives the production of mitochondrial reactive oxygen species (mROS) that ultimately influences HIF-1α stabilization. Moreover, STING increases the intracellular succinate concentration in infected macrophages, and succinate pretreatment induces HIF-1α stabilization and IL-1β release independently of its cognate receptor GPR91. Collectively, these data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during B. abortus infection that is orchestrated by STING via HIF-1α pathway and highlight the metabolic reprogramming of macrophages as a potential treatment strategy for bacterial infections.","journal":"PLoS Pathogens","year":2021,"id":149461,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":106,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316747,"name":"Erika S. Guimarães","orcid":"0000-0002-1893-3592","position":1,"is_corresponding":false},{"id":369631,"name":"Fábio V. Marinho","orcid":"0000-0001-6885-3438","position":2,"is_corresponding":false},{"id":635996,"name":"Isabella Figueiredo Assis Macedo","orcid":"0000-0001-9891-5935","position":3,"is_corresponding":false},{"id":468114,"name":"Eric Roberto Guimarães Rocha Aguiar","orcid":"0000-0002-8143-5756","position":4,"is_corresponding":false},{"id":395491,"name":"Glen N. Barber","orcid":"0000-0002-4703-0931","position":5,"is_corresponding":false},{"id":635997,"name":"Pedro M. Moraes‐Vieira","orcid":"0000-0002-8263-786X","position":6,"is_corresponding":false},{"id":516113,"name":"José C. Alves‐Filho","orcid":"0000-0002-9918-8714","position":7,"is_corresponding":false},{"id":269886,"name":"Sérgio C. Oliveira","orcid":"0000-0003-4062-5577","position":8,"is_corresponding":false},{"id":316746,"name":"Marco Túlio R. Gomes","orcid":"0000-0002-9701-0808","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:42:56.251607Z","pmid":"33989349","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}