ArticlemBio2021
The Tumor Necrosis Factor Alpha and Interleukin 6 Auto-paracrine Signaling Loop Controls Mycobacterium avium Infection via Induction of IRF1/IRG1 in Human Primary Macrophages.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- The Cyclooxygenase 2 Inhibitor Etoricoxib as Adjunctive Therapy in Tuberculosis Impairs Macrophage Control of Mycobacterial Growth.The Journal of infectious diseases · 2024Trial
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Human pneumovirus induces IFN-dependent expression of the immune-responsive gene 1 and is inhibited by 4-octyl itaconate in human macrophages.NAR molecular medicine · 2026Article
- ACOD1 expression in patients with sepsis: an exploratory study of associations with disease severity and immune signatures.BMC infectious diseases · 2026Article
- Will It Be Possible in the Future to Target Innate Immunity Against Staphylococcus aureus Using Resident Microbiota and Plant Extracts?Journal of immunology research · 2026Article
- Characterization of novel mycobacteriophages with a focus on phage Pisa4 and its interaction with human innate immune cells.Frontiers in microbiology · 2026Article
- Fullerene Gallium Phosphonate Shows Antimycobacterial Effect AgainstInternational journal of molecular sciences · 2025Article
- Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Itaconate and its derivatives as anti-pathogenic agents.RSC advances · 2025Review
- Recurrent NTM pulmonary disease despite avoidance of hot spring exposure in a plaque psoriasis patient treated with Secukinumab: a case report.BMC infectious diseases · 2025Article
- Enhanced recovery after surgery in the perioperative period promotes recovery of cervical cancer patients undergoing transabdominal radical resection.American journal of translational research · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Role of Type I Interferons duringBiomolecules · 2024Review
- Effect and Mechanism of Mycobacterium avium MAV-5183 on Apoptosis of Mouse Ana-1 Macrophages.Cell biochemistry and biophysics · 2024Article
- Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.Science advances · 2024Article
- Divergent effects of itaconate isomers onFrontiers in immunology · 2024Article
- Metformin improvesFrontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages sense and respond to pathogens by induction of antimicrobial and inflammatory programs to alert other immune cells and eliminate the infectious threat. We have previously identified the transcription factor IRF1 to be consistently activated in macrophages during Mycobacterium avium infection, but its precise role during infection is not clear. Here, we show that tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) autocrine/paracrine signaling contributes to controlling the intracellular growth of M. avium in human primary macrophages through activation of IRF1 nuclear translocation and expression of IRG1, a mitochondrial enzyme that produces the antimicrobial metabolite itaconate. Small interfering RNA (siRNA)-mediated knockdown of IRF1 or IRG1 increased the mycobacterial load, whereas exogenously provided itaconate was bacteriostatic at high concentrations. While the overall level of endogenous itaconate was low in M. avium-infected macrophages, the repositioning of mitochondria to M. avium phagosomes suggests a mechanism by which itaconate can be delivered directly to M. avium phagosomes in sufficient quantities to inhibit growth. Using mRNA hybridization, we further show that uninfected bystander cells actively contribute to the resolution of infection by producing IL-6 and TNF-α, which, via paracrine signaling, activate IRF1/IRG1 and strengthen the antimicrobial activity of infected macrophages. This mechanism contributes to the understanding of why patients on anti-inflammatory treatment, e.g., with tocilizumab or infliximab, can be more susceptible to mycobacterial disease.
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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.