ArticleNature microbiology2020
Extracellular SQSTM1 mediates bacterial septic death in mice through insulin receptor signalling.
Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
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- BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis.Cellular & molecular biology letters · 2025Review
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification.Cell communication and signaling : CCS · 2025Article
- A neuroimmune pathway drives bacterial infection.Science advances · 2025Article
- Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance.Molecular cancer · 2025Review
- Value of animal sepsis research in navigating the translational labyrinth.Frontiers in immunology · 2025Article
- Comprehensive characterization of multi-omics landscapes between gut microbial metabolites and the druggable genome in sepsis.Frontiers in immunology · 2025Article
- Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.Autophagy · 2024Article
- The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.MedComm · 2024Review
- PIKfyve controls dendritic cell function and tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.Nature communications · 2024Article
- p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot-Marie-Tooth disease type 1A.Scientific reports · 2024Article
- Caspase-5: Structure, Pro-Inflammatory Activity and Evolution.Biomolecules · 2024Review
- The lipid basis of cell death and autophagy.Autophagy · 2024Review
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12 authors at 8 institutions in 4 countries.
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Abstract
Sepsis is the most common cause of death for patients in intensive care worldwide due to a dysregulated host response to infection. Here, we investigate the role of sequestosome-1 (SQSTM1/p62), an autophagy receptor that functions as a regulator of innate immunity, in sepsis. We find that lipopolysaccharide elicits gasdermin D-dependent pyroptosis to enable passive SQSTM1 release from macrophages and monocytes, whereas transmembrane protein 173-dependent TANK-binding kinase 1 activation results in the phosphorylation of SQSTM1 at Ser403 and subsequent SQSTM1 secretion from macrophages and monocytes. Moreover, extracellular SQSTM1 binds to insulin receptor, which in turn activates a nuclear factor kappa B-dependent metabolic pathway, leading to aerobic glycolysis and polarization of macrophages. Intraperitoneal injection of anti-SQSTM1-neutralizing monoclonal antibodies or conditional depletion of Insr in myeloid cells using the Cre-loxP system protects mice from lethal sepsis (caecal ligation and puncture or infection by Escherichia coli or Streptococcus pneumoniae) and endotoxaemia. We also report that circulating SQSTM1 and the messenger RNA expression levels of SQSTM1 and INSR in peripheral blood mononuclear cells are related to the severity of sepsis in 40 patients. Thus, extracellular SQSTM1 has a pathological role in sepsis and could be targeted to develop therapies for sepsis.
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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.