ArticleCell death discovery2016
Hypoxia and classical activation limits Mycobacterium tuberculosis survival by Akt-dependent glycolytic shift in macrophages.
Article in Cell death discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Tuberculosis and Cellular Metabolism: Insights into the Crosstalk Between Macrophage Immunometabolism and Muscle Dysregulation.International journal of molecular sciences · 2026Review
- Protein Kinase C δ: a critical hub regulating macrophage immunomodulatory functions duringbioRxiv : the preprint server for biology · 2025Article
- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- Glucose Metabolic Reprogramming of Macrophages AgainstImmunoTargets and therapy · 2025Review
- Clinical characteristics and pregnancy outcomes in pregnant women with TB: a retrospective cohort study.Annals of medicine · 2024Article
- The Role of mTOR inBiomedicines · 2024Review
- TheFrontiers in immunology · 2024Article
- TheMicroorganisms · 2023Article
- Role of NF-κB duringInternational journal of molecular sciences · 2023Review
- GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection.The Journal of experimental medicine · 2022Article
- Article
- Lactate cross-talk in host-pathogen interactions.The Biochemical journal · 2021Review
- Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches.Frontiers in immunology · 2021Review
- Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis.Nature communications · 2020Article
- AMPK-Targeted Effector Networks in Mycobacterial Infection.Frontiers in microbiology · 2019Review
- Immunometabolism of Phagocytes DuringFrontiers in molecular biosciences · 2019Review
- Article
- Modeling Host-Pathogen Interaction to Elucidate the Metabolic Drug Response of IntracellularFrontiers in cellular and infection microbiology · 2019Article
- Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn's disease, in comparison to intestinal tuberculosis.Intestinal research · 2018Article
- Selective Autophagy and Xenophagy in Infection and Disease.Frontiers in cell and developmental biology · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular reactive oxygen species (ROS) is a major antibacterial defense mechanism used by macrophages upon activation. Exposure of Mycobacterium tuberculosis (Mtb)-infected macrophages to hypoxia is known to compromise the survival of the pathogen. Here we report that the hypoxia-induced control of intracellular Mtb load in RAW 264.7 macrophages was mediated by regulating the cellular ROS levels. We show that similar to classical activation, hypoxia incubation of macrophages resulted in decreased mitochondrial outer membrane potential (MOMP) and a concomitant increase in the cellular ROS levels. Mitochondrial depolarization and consequently higher ROS could be blocked by knocking down Akt using siRNAs, which acted by inhibiting the switch to glycolytic mode of metabolism, an essential adaptive response upon classical activation or hypoxic incubation of macrophages. Moreover, in the classically activated macrophages or in the macrophages under hypoxia incubation, supplementation with additional glucose had similar effects as Akt knockdown. Interestingly, in both the cases, the reversal of phenotype was linked with the ability of the mitochondrial F0-F1 ATP synthase activity to maintain the MOMP in the absence of oxidative phosphorylation. Both Akt knockdown and glucose supplementation were also able to rescue Mtb survival in these macrophages upon classical activation or hypoxia incubation. These results provide a framework for better understanding of how the interplay between oxygen supply, which is limiting in the human tubercular granulomas, and nutrient availability could together direct the outcome of infections in vivo.
Identifiers
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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.