ArticleCellular microbiology2016
Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection.
Article in Cellular microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Heme Oxygenase-1 Differentially Controls Pigmentation in Physiological and Pathological Melanogenesis.Pigment cell & melanoma research · 2026Article
- CD73Nature communications · 2026Article
- Non-TyphoidalInfectious disease reports · 2026Article
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Effects and mechanisms of Salmonella plasmid virulence gene spv on host-regulated cell death.Current microbiology · 2024Review
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- CD4Science advances · 2023Article
- Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections.Wellcome open research · 2023Review
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies.Journal of nanobiotechnology · 2022Review
- Limited Heme Oxygenase Contribution to Modulating the Severity ofAntioxidants (Basel, Switzerland) · 2022Article
- Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease.Frontiers in pharmacology · 2022Review
- Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation duringAntioxidants (Basel, Switzerland) · 2021Article
- Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders.Advanced drug delivery reviews · 2021Review
- Regulation of inflammation by the antioxidant haem oxygenase 1.Nature reviews. Immunology · 2021Review
- Leishmania donovani Targets Host Transcription Factor NRF2 To Activate Antioxidant Enzyme HO-1 and Transcriptional Repressor ATF3 for Establishing Infection.Infection and immunity · 2021Article
- Heme Oxygenase-1 as a Pharmacological Target for Host-Directed Therapy to Limit Tuberculosis Associated Immunopathology.Antioxidants (Basel, Switzerland) · 2021Review
- Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen.Cell reports · 2021Article
- Immune Modulation by Inhibitors of the HO System.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Macrophages are central for the immune control of intracellular microbes. Heme oxygenase 1 (HO-1, hmox) is the first and rate limiting enzyme in the breakdown of heme originating from degraded senescent erythrocytes and heme-proteins, yielding equal amounts of iron, carbon monoxide and biliverdin. HO-1 is strongly up-regulated in macrophages in response to inflammatory signals, including bacterial endotoxin. In view of the essential role of iron for the growth and proliferation of intracellular bacteria along with known effects of the metal on innate immune function, we examined whether HO-1 plays a role in the control of infection with the intracellular bacterium Salmonella Typhimurium. We studied the course of infection in stably-transfected murine macrophages (RAW264.7) bearing a tetracycline-inducible plasmid producing hmox shRNA and in primary HO-1 knockout macrophages. While uptake of bacteria into macrophages was not affected, a significantly reduced survival of intracellular Salmonella was observed upon hmox knockdown or pharmacological hmox inhibition, which was independent of Nramp1 functionality. This could be traced to limitation of iron availability for intramacrophage bacteria along with enhanced stimulation of innate immune effector pathways, including the formation of reactive oxygen and nitrogen species and increased TNF-α expression. Mechanistically, these latter effects result from intracellular iron limitation with subsequent activation of NF-κB and further inos, tnfa and p47phox transcription along with reduced formation of the anti-inflammatory and radical scavenging molecules, CO and biliverdin as a consequence of HO-1 silencing. Taken together our data provide novel evidence that the infection-driven induction of HO-1 exerts detrimental effects in the early control of Salmonella infection, whereas hmox inhibition can favourably modulate anti-bacterial immune effector pathways of macrophages and promote bacterial elimination.
Indexed as
Identifiers
What OpenQuestion holds
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.