ArticleThe Journal of clinical investigation2014
Macrophages sense and kill bacteria through carbon monoxide-dependent inflammasome activation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 181 citations in OpenAlex.
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Engineering a multifunctional nanoplatform with cascade catalytic and bidirectional immunomodulatory capacities for integrating sepsis therapy.Journal of advanced research · 2026Article
- A Cathepsin B-Triggered CO-Releasing Molecule with a Non-Toxic Metal Core for Targeted Tumor Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Organic Carbon Monoxide Prodrugs Activated by Endogenous Reactive Oxygen Species for Targeted Delivery.Journal of the American Chemical Society · 2025Article
- Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.Medicinal research reviews · 2025Review
- Carbon monoxide potentiates the effect of corticosteroids in suppressing inflammatory responses in cell culture.Bioorganic & medicinal chemistry · 2025Article
- Carbon Monoxide and Prokaryotic Energy Metabolism.International journal of molecular sciences · 2025Review
- Pyroptosis: A Novel Therapeutic Target for Bioactive Compounds in Human Disease Treatment? A Narrative Review.Nutrients · 2025Review
- Gas-Generating Photocatalytic Agents for Bacterial Infection Treatment.Research (Washington, D.C.) · 2025Review
- Effects of Low-Dose Carbon Monoxide on Antibiotic Efficacy.microPublication biology · 2025Article
- Micron-scale topographies affect phagocytosis of bacterial cells on polydimethylsiloxane surfaces.Acta biomaterialia · 2024Article
- Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2024Article
- Membrane-Bound Redox Enzyme CytochromeInternational journal of molecular sciences · 2024Article
- Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.Frontiers in immunology · 2024Article
- Article
- The pseudokinase MLKL contributes to host defense againstVirulence · 2023Article
- Heme Oxygenase-1 and Its Role in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Ozone as an Nrf2-Keap1-ARE Activator in the Anti-Microbial Activity and Immunity Modulation of Infected Wounds.Antioxidants (Basel, Switzerland) · 2023Article
- Theaflavin mitigates acute gouty peritonitis and septic organ injury in mice by suppressing NLRP3 inflammasome assembly.Acta pharmacologica Sinica · 2023Article
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Microbial clearance by eukaryotes relies on complex and coordinated processes that remain poorly understood. The gasotransmitter carbon monoxide (CO) is generated by the stress-responsive enzyme heme oxygenase-1 (HO-1, encoded by Hmox1), which is highly induced in macrophages in response to bacterial infection. HO-1 deficiency results in inadequate pathogen clearance, exaggerated tissue damage, and increased mortality. Here, we determined that macrophage-generated CO promotes ATP production and release by bacteria, which then activates the Nacht, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome, intensifying bacterial killing. Bacterial killing defects in HO-1-deficient murine macrophages were restored by administration of CO. Moreover, increased CO levels enhanced the bacterial clearance capacity of human macrophages and WT murine macrophages. CO-dependent bacterial clearance required the NALP3 inflammasome, as CO did not increase bacterial killing in macrophages isolated from NALP3-deficient or caspase-1-deficient mice. IL-1β cleavage and secretion were impaired in HO-1-deficient macrophages, and CO-dependent processing of IL-1β required the presence of bacteria-derived ATP. We found that bacteria remained viable to generate and release ATP in response to CO. The ATP then bound to macrophage nucleotide P2 receptors, resulting in activation of the NALP3/IL-1β inflammasome to amplify bacterial phagocytosis by macrophages. Taken together, our results indicate that macrophage-derived CO permits efficient and coordinated regulation of the host innate response to invading microbes.
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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.