ArticlePLoS pathogens2016
Activity of Uncleaved Caspase-8 Controls Anti-bacterial Immune Defense and TLR-Induced Cytokine Production Independent of Cell Death.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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Who cites it
65 citing papers in PubMed, 98 citations in OpenAlex.
- Mapping the holonomic signaling network that drives pathological changes in endotoxic shock.Cellular & molecular immunology · 2026Article
- Caspase-8-mediated CYLD cleavage boosts LPS-induced endotoxic shock.Cell death and differentiation · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Role of the two-pore domain potassium channel TREK-1 in hyperoxia- and mechanical stretch-induced alveolar epithelial injury.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Caspase-8 expression in CD8Science advances · 2025Article
- Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.Nature communications · 2025Article
- Article
- Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages.PLoS pathogens · 2024Article
- Distinct sequential death complexes regulate pyroptosis and IL-1β release in response toScience advances · 2024Article
- Caspase-8 activity mediates TNFα production and restrictsInfection and immunity · 2024Article
- Caspase-8-mediated inflammation but not apoptosis drives death of retinal ganglion cells and loss of visual function in glaucomaa.Research square · 2024Article
- cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.Journal of neuroinflammation · 2024Article
- Phosphorylation of caspase-8 by RSKs via organ-constrained effects controls the sensitivity to TNF-induced death.Cell death discovery · 2024Article
- N4BP1 coordinates ubiquitin-dependent crosstalk within the IκB kinase family to limit Toll-like receptor signaling and inflammation.Immunity · 2024Article
- A1 is induced by pathogen ligands to limit myeloid cell death and NLRP3 inflammasome activation.EMBO reports · 2023Article
- Caspase-8 inhibition improves the outcome of bacterial infections in mice by promoting neutrophil activation.Cell reports. Medicine · 2023Article
- TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection.PLoS pathogens · 2023Article
- Apoptotic proteins with non-apoptotic activity: expression and function in cancer.Apoptosis : an international journal on programmed cell death · 2023Review
- The host-directed therapeutic imatinib mesylate accelerates immune responses to Mycobacterium marinum infection and limits pathology associated with granulomas.PLoS pathogens · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Caspases regulate cell death programs in response to environmental stresses, including infection and inflammation, and are therefore critical for the proper operation of the mammalian immune system. Caspase-8 is necessary for optimal production of inflammatory cytokines and host defense against infection by multiple pathogens including Yersinia, but whether this is due to death of infected cells or an intrinsic role of caspase-8 in TLR-induced gene expression is unknown. Caspase-8 activation at death signaling complexes results in its autoprocessing and subsequent cleavage and activation of its downstream apoptotic targets. Whether caspase-8 activity is also important for inflammatory gene expression during bacterial infection has not been investigated. Here, we report that caspase-8 plays an essential cell-intrinsic role in innate inflammatory cytokine production in vivo during Yersinia infection. Unexpectedly, we found that caspase-8 enzymatic activity regulates gene expression in response to bacterial infection as well as TLR signaling independently of apoptosis. Using newly-generated mice in which caspase-8 autoprocessing is ablated (Casp8DA/DA), we now demonstrate that caspase-8 enzymatic activity, but not autoprocessing, mediates induction of inflammatory cytokines by bacterial infection and a wide variety of TLR stimuli. Because unprocessed caspase-8 functions in an enzymatic complex with its homolog cFLIP, our findings implicate the caspase-8/cFLIP heterodimer in control of inflammatory cytokines during microbial infection, and provide new insight into regulation of antibacterial immune defense.
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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.