ArticleInfection and immunity2012
Hypoxia-mediated impairment of the mitochondrial respiratory chain inhibits the bactericidal activity of macrophages.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 36 citations in OpenAlex.
- Sex-Based Differences in 90-Day Postoperative Complications Among Anemic Total Hip Arthroplasty Patients.Arthroplasty today · 2026Article
- Self-cascade oxygen-generating hydrogel/nanofibrous membrane composites restore periodontal microenvironment homeostasis.Journal of nanobiotechnology · 2026Article
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- OFrontiers in cellular and infection microbiology · 2025Article
- Mechanisms and Effects of Macrophage Polarization and Its Specifics in Pulmonary Environment.Physiological research · 2023Review
- Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective.Antioxidants (Basel, Switzerland) · 2022Review
- Bovine milk exosomes affected proliferation of macrophages under hypoxia.Current research in food science · 2022Article
- Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.Frontiers in physiology · 2022Review
- Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions.Cellular and molecular life sciences : CMLS · 2021Review
- Response to Oxidative Burst-Induced Hypoxia Is Associated With Macrophage Inflammatory Profiles as Revealed by Cellular Genome-Wide Association.Frontiers in immunology · 2021Article
- HIF1A and NFAT5 coordinate NaAutophagy · 2019Article
- Longitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils.Scientific reports · 2019Article
- Indoleamine 2,3-dioxygenase expression regulates the survival and proliferation of Fusobacterium nucleatum in THP-1-derived macrophages.Cell death & disease · 2018Article
- Parkinsonian Neurotoxins Impair the Pro-inflammatory Response of Glial Cells.Frontiers in molecular neuroscience · 2018Article
- Hypoxia, Hypoxia-Inducible Factor-1α, and Innate Antileishmanial Immune Responses.Frontiers in immunology · 2018Review
- Article
- Investigation of sinonasal microbiome spatial organization in chronic rhinosinusitis.International forum of allergy & rhinology · 2017Article
- Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses.Frontiers in immunology · 2017Article
- Th17 Polarization under Hypoxia Results in Increased IL-10 Production in a Pathogen-Independent Manner.Frontiers in immunology · 2017Article
- Myeloid Cell-Derived HIF-1α Promotes Control of Leishmania major.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In infected tissues oxygen tensions are low. As innate immune cells have to operate under these conditions, we analyzed the ability of macrophages (Mφ) to kill Escherichia coli or Staphylococcus aureus in a hypoxic microenvironment. Oxygen restriction did not promote intracellular bacterial growth but did impair the bactericidal activity of the host cells against both pathogens. This correlated with a decreased production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates. Experiments with phagocyte NADPH oxidase (PHOX) and inducible NO synthase (NOS2) double-deficient Mφ revealed that in E. coli- or S. aureus-infected cells the reduced antibacterial activity during hypoxia was either entirely or partially independent of the diminished PHOX and NOS2 activity. Hypoxia impaired the mitochondrial activity of infected Mφ. Inhibition of the mitochondrial respiratory chain activity during normoxia (using rotenone or antimycin A) completely or partially mimicked the defective antibacterial activity observed in hypoxic E. coli- or S. aureus-infected wild-type Mφ, respectively. Accordingly, inhibition of the respiratory chain of S. aureus-infected, normoxic PHOX(-/-) NOS2(-/-) Mφ further raised the bacterial burden of the cells, which reached the level measured in hypoxic PHOX(-/-) NOS2(-/-) Mφ cultures. Our data demonstrate that the reduced killing of S. aureus or E. coli during hypoxia is not simply due to a lack of PHOX and NOS2 activity but partially or completely results from an impaired mitochondrial antibacterial effector function. Since pharmacological inhibition of the respiratory chain raised the generation of ROI but nevertheless phenocopied the effect of hypoxia, ROI can be excluded as the mechanism underlying the antimicrobial activity of mitochondria.
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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.