ArticleImmunology2014
Autophagy activation by interferon-γ via the p38 mitogen-activated protein kinase signalling pathway is involved in macrophage bactericidal activity.
Article in Immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- By dawn or dusk-how circadian timing rewrites bacterial infection outcomes.FEBS letters · 2026Review
- Neutrophilic granule protein promotes lipopolysaccharide-induced iNOS/NO expression via JAK2/STAT1 signaling pathway and augments bacteria clearance of macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence.Communications biology · 2025Article
- Uncovering new insights into the role of the ubiquitin ligase Smurf1 on the regulation of innate immune signaling and resistance to infection.Frontiers in immunology · 2023Review
- FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer.PeerJ · 2023Article
- PGC-1α and MEF2 Regulate the Transcription of the Carnitine Transporter OCTN2 Gene in C2C12 Cells and in Mouse Skeletal Muscle.International journal of molecular sciences · 2022Article
- MAPK inhibitors protect against early‑stage osteoarthritis by activating autophagy.Molecular medicine reports · 2021Article
- Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.Molecular neurobiology · 2021Article
- Intraperitoneal injection of IFN-γ restores microglial autophagy, promotes amyloid-β clearance and improves cognition in APP/PS1 mice.Cell death & disease · 2020Article
- Nasal Pneumococcal Density Is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.American journal of respiratory and critical care medicine · 2020Article
- Review: the Role and Mechanisms of Macrophage Autophagy in Sepsis.Inflammation · 2019Review
- The Interferon-Gamma Paradox in Cancer.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- The immune characterization of interferon-β responses in tuberculosis patients.Microbiology and immunology · 2018Article
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- Current prospects of type II interferon γ signaling and autoimmunity.The Journal of biological chemistry · 2017Review
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- Interferon regulatory factor-1 activates autophagy to aggravate hepatic ischemia-reperfusion injury via the P38/P62 pathway in mice.Scientific reports · 2017Article
- Autophagy-associated immune responses and cancer immunotherapy.Oncotarget · 2016Review
- Fine-tuning of macrophage activation using synthetic rocaglate derivatives.Scientific reports · 2016Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages are involved in many essential immune functions. Their role in cell-autonomous innate immunity is reinforced by interferon-γ (IFN-γ), which is mainly secreted by proliferating type 1 T helper cells and natural killer cells. Previously, we showed that IFN-γ activates autophagy via p38 mitogen-activated protein kinase (p38 MAPK), but the biological importance of this signalling pathway has not been clear. Here, we found that macrophage bactericidal activity increased by 4 hr after IFN-γ stimulation. Inducible nitric oxide synthase (NOS2) is a major downstream effector of the Janus kinase-signal transducer and activator of transcription 1 signalling pathway that contributes to macrophage bactericidal activity via nitric oxide (NO) generation. However, no NO generation was observed after 4 hr of IFN-γ stimulation, and macrophage bactericidal activity at early stages after IFN-γ stimulation was not affected by the NOS inhibitors, NG-methyl-l-arginine acetate salt and diphenyleneiodonium chloride. These results suggest that an NOS2-independent signalling pathway is involved in IFN-γ-mediated bactericidal activity. We also found that this macrophage activity was attenuated by the addition of the p38 MAPK inhibitors, PD 169316, SB 202190, and SB 203580, or by the expression of short hairpin RNA against p38α or the essential factors for autophagy, Atg5 and Atg7. Collectively, our results suggest that the IFN-γ-mediated autophagy via p38 MAPK, without the involvement of NOS2, also contributes to the ability of macrophages to kill intracellular bacteria. These observations provide direct evidence that p38 MAPK-mediated autophagy can support IFN-γ-mediated cell-autonomous innate immunity.
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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.