ArticleJournal of immunology (Baltimore, Md. : 1950)2016
HIF-1α Is an Essential Mediator of IFN-γ-Dependent Immunity to Mycobacterium tuberculosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Type 2 diabetes mellitus associated microRNAs in tuberculosis susceptibility: a systematic review and bioinformatic analysis.Frontiers in endocrinology · 2026Pooled it
- Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test/interferon-γ release assay conversion.The Journal of clinical investigation · 2021Trial
- Plasma LOX-Products and Monocyte Signaling Is Reduced by Adjunctive Cyclooxygenase-2 Inhibitor in a Phase I Clinical Trial of Tuberculosis Patients.Frontiers in cellular and infection microbiology · 2021Trial
- Methylglyoxal AttenuatesInternational journal of molecular sciences · 2026Article
- Differential activation of NF-Κβ and HIF-1α between fetal liver-derived and myeloid-derived macrophages drives inflammatory differences followingInfection and immunity · 2026Article
- Mycobacterium tuberculosis MEM39 (Rv1977) hijacks host aldolase A (ALDOA) to subvert immunometabolism to facilitate bacterial intracellular survival.Cellular & molecular immunology · 2026Article
- Mitochondrial reactive oxygen species regulate HIF-1α stabilization and methylglyoxal accumulation in classically activated mouse macrophages.Immunometabolism (Cobham, Surrey) · 2026Review
- Integrative single-cell profiling and explainable AI identify monocyte-metabolic signatures as diagnostic biomarkers and candidate therapeutic targets in tuberculosis.Archives of microbiology · 2026Article
- Cas9eLife · 2026Article
- IL-36γ enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis via the IFN-γ/HIF-1ɑ/glycolysis pathway.Respiratory research · 2026Article
- Glycolysis inhibition in tuberculosis-driven metabolic rewiring reduces HIV-1 spread in macrophages.Life science alliance · 2026Article
- High-throughput characterization of Mycobacterium tuberculosis gene function across diverse conditions.PLoS biology · 2026Article
- IFN-γ-induced trained immunity enhances killing of priority pathogens in healthy and genetically vulnerable individuals.JCI insight · 2026Article
- Macrophage adaptation to hypoxia in the tuberculous granuloma potentiates mycobacterium-induced mitochondrial damage and granuloma necrosis.bioRxiv : the preprint server for biology · 2026Article
- Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Nutritional risk status and related influencing factors in patients with tuberculosis complicated with type 2 diabetes mellitus.Frontiers in nutrition · 2026Article
- Cell envelope maintenance by PhoP is essential forProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis.Nature communications · 2025Article
- c-Myc Inhibits Macrophage Antimycobacterial Response in Mycobacterium tuberculosis Infection.The Journal of infectious diseases · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The cytokine IFN-γ coordinates macrophage activation and is essential for control of pathogens, including Mycobacterium tuberculosis However, the mechanisms by which IFN-γ controls M. tuberculosis infection are only partially understood. In this study, we show that the transcription factor hypoxia-inducible factor-1α (HIF-1α) is an essential mediator of IFN-γ-dependent control of M. tuberculosis infection both in vitro and in vivo. M. tuberculosis infection of IFN-γ-activated macrophages results in a synergistic increase in HIF-1α protein levels. This increase in HIF-1α levels is functionally important, as macrophages lacking HIF-1α are defective for IFN-γ-dependent control of infection. RNA-sequencing demonstrates that HIF-1α regulates nearly one-half of all IFN-γ-inducible genes during infection of macrophages. In particular, HIF-1α regulates production of important immune effectors, including inflammatory cytokines and chemokines, eicosanoids, and NO. In addition, we find that during infection HIF-1α coordinates a metabolic shift to aerobic glycolysis in IFN-γ-activated macrophages. We find that this enhanced glycolytic flux is crucial for IFN-γ-dependent control of infection in macrophages. Furthermore, we identify a positive feedback loop between HIF-1α and aerobic glycolysis that amplifies macrophage activation. Finally, we demonstrate that HIF-1α is crucial for control of infection in vivo as mice lacking HIF-1α in the myeloid lineage are strikingly susceptible to infection and exhibit defective production of inflammatory cytokines and microbicidal effectors. In conclusion, we have identified HIF-1α as a novel regulator of IFN-γ-dependent immunity that coordinates an immunometabolic program essential for control of M. tuberculosis infection in vitro and in vivo.
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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.