ArticleProceedings of the National Academy of Sciences of the United States of America2014
Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers.
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Who cites it
185 citing papers in PubMed, 297 citations in OpenAlex.
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Crosstalk of regulated cell death pathways in sepsis-associated acute kidney injury: implications for therapy.Frontiers in cell and developmental biology · 2026Review
- Caspase-8 expression in CD8Science advances · 2025Article
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- RIOK2 kinase regulates the translocation of the FADD-RIPK1-Caspase-8 complex to the ER and the cleavage of Gasdermin D to drive pyroptosis.Nature communications · 2025Article
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
- NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni.PLoS pathogens · 2025Article
- Raver1 linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Guards and decoys: RIPoptosome and inflammasome pathway regulators of bacterial effector-triggered immunity.PLoS pathogens · 2025Review
- A pan-family screen of nuclear receptors in immunocytes reveals ligand-dependent inflammasome control.Immunity · 2024Article
- TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CD14 is a decision-maker between Fas-mediated death and inflammation.Cell reports · 2024Article
- Gasdermins as evolutionarily conserved executors of inflammation and cell death.Nature cell biology · 2024Review
- Non-canonical autophosphorylation of RIPK1 drives timely pyroptosis to control Yersinia infection.Cell reports · 2024Article
- Influenza A virus infection activates caspase-8 to enhance innate antiviral immunity by cleaving CYLD and blocking TAK1 and RIG-I deubiquitination.Cellular and molecular life sciences : CMLS · 2024Article
- 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
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.
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