ArticleThe Journal of clinical investigation2021
The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- A mild photothermal-mediated neuroimmunomodulatory composite hydrogel reverses the inflammatory osteoclast precursor phenotype to promote osteoporotic bone defect healing.Bioactive materials · 2026Article
- Biogenesis of TNF-α-insights into proteostasis and inflammation.The FEBS journal · 2026Review
- IFN𝛾 and IFN𝛾 mimetics prevent IFN-I-mediated TB susceptibility by regulating iron metabolism and lipid peroxidation.bioRxiv : the preprint server for biology · 2026Article
- Elimination of senescent cells with senolytic drugs as adjunctive host-directed therapy reduces tuberculosis progression in mice.Nature communications · 2026Article
- MAPK signaling pathways in host immune regulation during Mycobacterium tuberculosis infection.Frontiers in immunology · 2026Review
- Levofloxacin-Catalase-PLGA Nanoparticles Potentiate Sonodynamic Therapy to Alleviate BCG-Induced Tuberculous Granulomas via PI3K/Akt/VEGF Pathway Suppression in Rats.International journal of nanomedicine · 2026Article
- Inhibition of integrated stress response by ISRIB promotes mouse and human primordial follicle activation via the mTOR pathway.Journal of assisted reproduction and genetics · 2025Article
- Host Translational Control by Stress Granules PromotesMedComm · 2025Article
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- Dysplastic lung repair fosters a tuberculosis-promoting microenvironment through maladaptive macrophage polarization.PLoS pathogens · 2025Article
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- PET imaging of mycobacterial infection: transforming the pipeline for tuberculosis drug development.Npj imaging · 2025Review
- Aberrant macrophage activation and maladaptive lung repair promote tuberculosis progression uniquely in the lung.bioRxiv : the preprint server for biology · 2025Article
- Cross-species transcriptomics translation reveals a role for the unfolded protein response in Mycobacterium tuberculosis infection.NPJ systems biology and applications · 2025Article
- The SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.bioRxiv : the preprint server for biology · 2025Article
- Immunological roads diverged: mapping tuberculosis outcomes in mice.Trends in microbiology · 2025Review
- Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.Current medicinal chemistry · 2025Review
- Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.American journal of respiratory and critical care medicine · 2024Review
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity.Circulation research · 2024Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
The mechanism by which only some individuals infected with Mycobacterium tuberculosis develop necrotic granulomas with progressive disease while others form controlled granulomas that contain the infection remains poorly defined. Mice carrying the sst1-suscepible (sst1S) genotype develop necrotic inflammatory lung lesions, similar to human tuberculosis (TB) granulomas, which are linked to macrophage dysfunction, while their congenic counterpart (B6) mice do not. In this study we report that (a) sst1S macrophages developed aberrant, biphasic responses to TNF characterized by superinduction of stress and type I interferon pathways after prolonged TNF stimulation; (b) the late-stage TNF response was driven via a JNK/IFN-β/protein kinase R (PKR) circuit; and (c) induced the integrated stress response (ISR) via PKR-mediated eIF2α phosphorylation and the subsequent hyperinduction of ATF3 and ISR-target genes Chac1, Trib3, and Ddit4. The administration of ISRIB, a small-molecule inhibitor of the ISR, blocked the development of necrosis in lung granulomas of M. tuberculosis-infected sst1S mice and concomitantly reduced the bacterial burden. Hence, induction of the ISR and the locked-in state of escalating stress driven by the type I IFN pathway in sst1S macrophages play a causal role in the development of necrosis in TB granulomas. Interruption of the aberrant stress response with inhibitors such as ISRIB may offer novel host-directed therapy strategies.
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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.