The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Inflammatory caspases are innate immune receptors for intracellular LPS
Abstract
The murine caspase-11 non-canonical inflammasome responds to various bacterial infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism underlying cytosolic LPS sensing and the responsible pattern recognition receptor are unknown. Here we show that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced cytotoxicity was mediated by human caspase-4 that could functionally complement murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and lipid A with high specificity and affinity. LPS associated with endogenous caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent oligomerization upon LPS binding, resulting in activation of the caspases. Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) could bind to caspase-4/11 but failed to induce their oligomerization and activation. LPS binding was mediated by the CARD domain of the caspase. Binding-deficient CARD-domain point mutants did not respond to LPS with oligomerization or activation and failed to induce pyroptosis upon LPS electroporation or bacterial infections. The function of caspase-4/5/11 represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation.
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In the citing paper
“Further experimental observations confirmed that CASP11, CASP4, and CASP5 trigger pyroptosis upon sensing cytosolic LPS [609 622–624], in monocytes as well as in other cell types [609, 625].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [609]
In the citing paper
“LPS-induced pyroptosis involves the physical interaction of LPS (or its lipid moiety) with the CARD domain of CASP11, CASP4, or CASP5, a highly specific binding resulting in caspase oligomerization and consequent activation [609].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [609]
In the citing paper
“(2) can also occur in cell types other than cells from the monocytic lineage [609]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [609]
In the citing paper
“Thus, CASP11, CASP4, and CASP5 act as bona fide PRRs for cytosolic LPS.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [609]
Citations
Cites
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Caspase Functions in Cell Death and DiseasePreprint
McIlwain, D. R., Berger, T., & Mak, T. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008656 · Cited by 2,702
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530
The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex
Park, B. S., Song, D. H., Kim, H. M., Choi, B., Lee, H., & Lee, J. (2009) · Nature · doi:10.1038/nature07830 · Cited by 2,513
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214
Molecular mechanisms of caspase regulation during apoptosis
Riedl, S. J., & Shi, Y. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1496 · Cited by 1,933
Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4
Kayagaki, N., Wong, M. T., Stowe, I. B., Ramani, S. R., Gonzalez, L. C., Akashi‐Takamura, S., Miyake, K., Zhang, J., Lee, W. P., Muszyński, A., et al. (2013) · Science · doi:10.1126/science.1240248 · Cited by 1,545
Mechanisms of caspase activation
Boatright, K. M., & Salvesen, G. S. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.009 · Cited by 1,374
Lipid A Modification Systems in Gram-Negative Bacteria
Raetz, C. R. H., Reynolds, C. M., Trent, M. S., & Bishop, R. E. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.010307.145803 · Cited by 1,371
The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus
Zhao, Y., Yang, J., Shi, J., Gong, Y., Lu, Q., Xu, H., Liu, L., & Shao, F. (2011) · Nature · doi:10.1038/nature10510 · Cited by 1,310
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Items 1,001–1,002 of 1,002
Zhang, X., Yang, X., Zhang, S., Wang, J., Wang, M., Ma, T., Wan, M., Lv, X., Yan, T., & Jia, Y. (2023) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgad014 · Cited by 10
New perspective for pathomechanism and clinical applications of animal toxins: Programmed cell death
Sun, J., Liu, J., Liu, M., Bi, X., & Huang, C. (2024) · Toxicon · doi:10.1016/j.toxicon.2024.108071 · Cited by 6
Metadata
- Authors
- Shi, J., Zhao, Y., Wang, Y., Gao, W., Ding, J., Li, P., Hu, L., & Shao, F.
- Affiliations
- Peking University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shao, Feng
- Venue
- Nature
- Published
- 2014-08-06
- Volume
- 514
- Issue
- 7521
- Pages
- 187-192
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2068619092
- Cited by
- 2,285
- References
- 41
- Citations by year
- 2026: 190 · 2025: 205 · 2024: 231 · 2023: 277 · 2022: 254 · 2021: 227 · 2020: 193 · 2019: 162 · 2018: 158 · 2017: 131 · 2016: 128 · 2015: 103 · 2014: 23
- FWCI
- 52.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Tsinghua University
- University of British Columbia
- National Key Research and Development Program of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- caspase-4, caspase-5, non-canonical inflammasome, pyroptosis, pattern recognition receptors, CARD domain, lipid A, endotoxic shock, intracellular bacterial infection, innate immunity, inflammatory cell death
- MeSH terms
- Animals, Cells, Cultured, Enzyme Activation, Epithelial Cells, Genetic Complementation Test, Humans, Immunity, Innate, Inflammation, Lipid A, Lipopolysaccharides, Macrophages, Necrosis, Protein Binding, Rhodobacter sphaeroides, Substrate Specificity, Keratinocytes, Cell Death, Caspases, Surface Plasmon Resonance, Mutant Proteins, Mice, Caspases, Initiator, Protein Multimerization
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