ArticleThe Journal of biological chemistry2013
Cathepsin-mediated necrosis controls the adaptive immune response by Th2 (T helper type 2)-associated adjuvants.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 74 citations in OpenAlex.
- The Role and Safety of Aluminum Adjuvants in Childhood Vaccines.Pediatrics · 2026Review
- Targeting Glycolysis with 2-Deoxy-D-Glucose and Lysosomal Integrity with L-Leucyl-L-Leucine Methyl Ester as Antimelanoma Strategy.Pharmaceutics · 2025Article
- Intracellular Delivery of Native Proteins by BioReversible Arginine Modification (BioRAM) on Amino Groups.Angewandte Chemie (International ed. in English) · 2025Article
- The role of cell death pathways in respiratory viral infection and vaccination: two sides of the same coin.Frontiers in immunology · 2025Review
- Crystalline silica induces macrophage necrosis and causes subsequent acute pulmonary neutrophilic inflammation.Cell biology and toxicology · 2022Article
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- Occupational Cement Dust Exposure and Inflammatory Nemesis: Bangladesh Relevance.Journal of inflammation research · 2021Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Article
- Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies.Frontiers in oncology · 2020Review
- BODIPY-Caged Photoactivated Inhibitors of Cathepsin B Flip the Light Switch on Cancer Cell Apoptosis.ACS chemical biology · 2019Article
- Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation.Frontiers in immunology · 2019Article
- The Outcome of theJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- How Inflammasomes Inform Adaptive Immunity.Journal of molecular biology · 2018Review
- Macrophage Recognition of Crystals and Nanoparticles.Frontiers in immunology · 2018Review
- Old and new adjuvants.Current opinion in immunology · 2017Review
- Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation.Journal of leukocyte biology · 2017Article
- Phagolysosome acidification is required for silica and engineered nanoparticle-induced lysosome membrane permeabilization and resultant NLRP3 inflammasome activity.Toxicology and applied pharmacology · 2017Article
- Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents.Journal of toxicology and environmental health. Part B, Critical reviews · 2017Review
- Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells.PloS one · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunologic adjuvants are critical components of vaccines, but it remains unclear how prototypical adjuvants enhance the adaptive immune response. Recent studies have shown that necrotic cells could trigger an immune response. Although most adjuvants have been shown to be cytotoxic, this activity has traditionally been considered a side effect. We set out to test the role of adjuvant-mediated cell death in immunity and found that alum, the most commonly used adjuvant worldwide, triggers a novel form of cell death in myeloid leukocytes characterized by cathepsin-dependent lysosome-disruption. We demonstrated that direct lysosome-permeabilization with a soluble peptide, Leu-Leu-OMe, mimics the alum-like form of necrotic cell death in terms of cathepsin dependence and cell-type specificity. Using a combination of a haploid genetic screen and cathepsin-deficient cells, we identified specific cathepsins that control lysosome-mediated necrosis. We identified cathepsin C as critical for Leu-Leu-OMe-induced cell death, whereas cathepsins B and S were required for alum-mediated necrosis. Consistent with a role of necrotic cell death in adjuvant effects, Leu-Leu-OMe replicated an alum-like immune response in vivo, characterized by dendritic cell activation, granulocyte recruitment, and production of Th2-associated antibodies. Strikingly, cathepsin C deficiency not only blocked Leu-Leu-OMe-mediated necrosis but also impaired Leu-Leu-OMe-enhanced immunity. Together our findings suggest that necrotic cell death is a powerful mediator of a Th2-associated immune response.
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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.