ArticleAutophagy2018
Antimycobacterial effect of IFNG (interferon gamma)-induced autophagy depends on HMOX1 (heme oxygenase 1)-mediated increase in intracellular calcium levels and modulation of PPP3/calcineurin-TFEB (transcription factor EB) axis.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- A Clinical Multicenter Trial of Recombinant Human Interferon Gamma in Tuberculosis (GAM2022): Experience with the Use of Human Recombinant Interferon Gamma in TB Practice.Infectious disorders drug targets · 2025Trial
- IFNγ blockade in Mycobacterium tuberculosis infected macaques alters the granuloma environment but not bacterial control.Nature communications · 2026Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Tacrolimus inhibits CVB3-targeted regulation of TFEB by PPP3/calcineurin.Frontiers in cellular and infection microbiology · 2026Article
- Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.Nature communications · 2025Article
- TFEB safeguards trophoblast syncytialization in humans and mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.PLoS pathogens · 2024Article
- Article
- Differential Regulation of TFEB-Induced Autophagy during Mtb Infection and Starvation.Microorganisms · 2023Review
- HO-1-Mediated Autophagic Restoration Protects Lens Epithelial Cells Against Oxidative Stress and Cellular Senescence.Investigative ophthalmology & visual science · 2023Article
- Autophagic reprogramming of bone marrow-derived macrophages.Immunologic research · 2023Article
- Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer.World journal of gastrointestinal oncology · 2023Article
- A NOVEL NOX/PHOX-CD38-NAADP-TFEB AXIS IMPORTANT FOR MACROPHAGE ACTIVATION DURING BACTERIAL PHAGOCYTOSIS.Autophagy · 2022Article
- Mycobacterial acyl carrier protein suppresses TFEB activation and upregulates miR-155 to inhibit host defense.Frontiers in immunology · 2022Article
- Hydrogen sulfide-induced GAPDH sulfhydration disrupts the CCAR2-SIRT1 interaction to initiate autophagy.Autophagy · 2021Article
- Autophagy and the Lysosomal System in Cancer.Cells · 2021Review
- Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections.Scientific reports · 2021Article
- MiT Family Transcriptional Factors in Immune Cell Functions.Molecules and cells · 2021Review
- Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis.Nature communications · 2021Article
- Heme Oxygenase-1 as a Pharmacological Target for Host-Directed Therapy to Limit Tuberculosis Associated Immunopathology.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO. Chelation of intracellular calcium inhibits IFNG-mediated autophagy and mycobacterial clearance from macrophages. Moreover, we show that IFNG-mediated increase in intracellular calcium leads to activation of the phosphatase calcineurin (PPP3), which dephosphorylates the TFEB (transcription factor EB) to induce autophagy. PPP3-mediated activation and nuclear translocation of TFEB are critical in IFNG-mediated mycobacterial trafficking and survival inside the infected macrophages. These findings establish that IFNG utilizes the PPP3-TFEB signaling axis for inducing autophagy and regulating mycobacterial growth. We believe this signaling axis could act as a therapeutic target for suppression of growth of intracellular pathogens.
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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.