ArticleProceedings of the National Academy of Sciences of the United States of America2015
Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 268 citations in OpenAlex.
- Review: the role of GSDMD in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- The cytokines interleukin-6 and interferon-α induce distinct microglia phenotypes.Journal of neuroinflammation · 2022Pooled it
- When folding CARDs wins the game: molecular snapshots of lipopolysaccharide sensing by the non-canonical inflammasome.Biochemical Society transactions · 2026Review
- What goes around comes around: updates in the study ofInfection and immunity · 2026Review
- Plant natural products targeting NLRP3 inflammasome in Parkinson's disease: Molecular activation and regulation to therapeutics.iScience · 2026Review
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Article
- Human non-canonical inflammasomes activate CASP3 to limit intracellular Salmonella replication in macrophages.PLoS pathogens · 2026Article
- Pyroptosis: mechanism and therapeutic strategies with intervertebral disc degeneration.Experimental & molecular medicine · 2026Review
- Extracellular Lipopolysaccharide Triggers the Release of Unconjugated Interferon-Stimulated Gene 15 (ISG15) Protein from Macrophages via Type-I Interferon/Caspase-4/Gasdermin-D Pathway.Pathogens (Basel, Switzerland) · 2026Article
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- Non-anticoagulant heparins: glycan-mediated immune modulation and therapeutic applications.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction-driven PANoptosis in doxorubicin-induced cardiotoxicity: mechanistic insights and intervention strategies.Frontiers in pharmacology · 2026Review
- Progress in the Treatment of Ulcerative Colitis by Targeting NLRP3 Inflammasome.Drug design, development and therapy · 2026Review
- Targeting pyroptosis in periodontitis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
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- Article
- Radiation meets inflammation: NLRP3 inflammasome at the core of radiation-induced cardiac injury.Journal of translational medicine · 2025Review
- Human non-canonical inflammasomes activate CASP3 to limit intracellularbioRxiv : the preprint server for biology · 2025Article
- Streptococcus pyogenes EVs induce the alternative inflammasome via caspase-4/-5 in human monocytes.EMBO reports · 2025Article
111 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Inflammasomes are critical for host defense against bacterial pathogens. In murine macrophages infected by gram-negative bacteria, the canonical inflammasome activates caspase-1 to mediate pyroptotic cell death and release of IL-1 family cytokines. Additionally, a noncanonical inflammasome controlled by caspase-11 induces cell death and IL-1 release. However, humans do not encode caspase-11. Instead, humans encode two putative orthologs: caspase-4 and caspase-5. Whether either ortholog functions similar to caspase-11 is poorly defined. Therefore, we sought to define the inflammatory caspases in primary human macrophages that regulate inflammasome responses to gram-negative bacteria. We find that human macrophages activate inflammasomes specifically in response to diverse gram-negative bacterial pathogens that introduce bacterial products into the host cytosol using specialized secretion systems. In primary human macrophages, IL-1β secretion requires the caspase-1 inflammasome, whereas IL-1α release and cell death are caspase-1-independent. Instead, caspase-4 mediates IL-1α release and cell death. Our findings implicate human caspase-4 as a critical regulator of noncanonical inflammasome activation that initiates defense against bacterial pathogens in primary human macrophages.
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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.