ArticlePLoS pathogens2021
STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 92 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Natural Products Targeting Airway Inflammation and Mucus Hypersecretion: Molecular Mechanisms and Therapeutic Potential for Respiratory Health.Nutrients · 2026Review
- TLR9 DNA methylation and gene expression in cattle naturally infected with B. abortus.Tropical animal health and production · 2026Article
- Research Progress on Downstream Mechanisms of Glucose Metabolic Reprogramming and Its Role in the Occurrence and Progression of Type 2 Diabetes Mellitus.Biomedicines · 2026Review
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- STING signalling as a mediator between lipid metabolism and innate immunity.Nature reviews. Molecular cell biology · 2026Article
- Comprehensive genomic identification of essential genes required for Brucella melitensis intracellular survival during macrophage infection.Scientific reports · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Metabolic map of Brucellosis: From acute and chronic phase adaptation to targeted nanodrug design.Materials today. Bio · 2026Review
- The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor.Journal of translational medicine · 2026Review
- Paclitaxel induces trained immunity via the GPR183-STING axis to enhance host defense against MRSA infection.Veterinary research · 2026Article
- Brucella abortus infection exploits ZDHHC3-mediated STAT3 palmitoylation to regulate host responses and promote persistence.Veterinary research · 2026Article
- Targeting cGAS-STING-macrophage axis: a novel therapeutic horizon for renal fibrosis.Frontiers in immunology · 2026Review
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- Integrated clinical and PBMC transcriptomic profiling identifies lipid metabolism-related candidate signatures associated with chronic brucellosis.Frontiers in cellular and infection microbiology · 2026Article
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- A review of current evidence and perspectives on the mechanisms and clinical significance of hypoxia-induced remodeling of the gastric microbiota-metabolism axis.Frontiers in microbiology · 2026Review
- Molecular Mechanisms of cGAS-STING Axis and Mitochondrial Dysfunction-Related Diseases in Humans: A Comprehensive Review.Current neuropharmacology · 2026Review
- Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.Journal of inflammation research · 2026Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.