The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Activation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation
Open accessAbstract
Despite its clinical importance in infection and autoimmunity, the activation mechanisms of the NLRP1b inflammasome remain enigmatic. Here we show that deletion of the inflammasome adaptor ASC in BALB/c mice and in C57BL/6 macrophages expressing a functional NLRP1b prevents anthrax lethal toxin (LeTx)-induced caspase-1 autoproteolysis and speck formation. However, ASC−/− macrophages undergo normal LeTx-induced pyroptosis and secrete significant amounts of interleukin (IL)-1β. In contrast, ASC is critical for caspase-1 autoproteolysis and IL-1β secretion by the NLRC4, NLRP3 and AIM2 inflammasomes. Notably, LeTx-induced inflammasome activation is associated with caspase-1 ubiquitination, which is unaffected in ASC-deficient cells. In vivo, ASC-deficient mice challenged with LeTx produce significant levels of IL-1β, IL-18 and HMGB1 in circulation, although caspase-1 autoproteolysis is abolished. As a result, ASC−/− mice are sensitive to rapid LeTx-induced lethality. Together, these results demonstrate that ASC-driven caspase-1 autoprocessing and speck formation are dispensable for the activation of caspase-1 and the NLRP1b inflammasome. The NLRP1b inflammasome activation may lead to pyroptosis and secretion of the inflammatory cytokines IL-1ß and IL-18 but the mechanisms behind these processes are not fully understood. Here, the authors show that they can occur independently of the inflammasome adaptor ASC and without caspase-1 autoprocessing.
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Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
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
Self-citationThe AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Rathinam, V. A. K., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1864 · Cited by 1,331
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935
Self-citationde Rivero Vaccari, J. P., Lotocki, G., Alonso, O. F., Bramlett, H. M., Dietrich, W. D., & Keane, R. W. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.46 · Cited by 312
Cited by
Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion
He, W.-T., Wan, H., Hu, L., Chen, P., Wang, X., Huang, Z., Yang, Z.-H., Zhong, C.-Q., & Han, J. (2015) · Cell Research · doi:10.1038/cr.2015.139 · Cited by 2,517
Pyroptotic cell death defends against intracellular pathogens
Jorgensen, I., & Miao, E. A. (2015) · Immunological Reviews · doi:10.1111/imr.12287 · Cited by 1,021
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956
Inflammasomes in neuroinflammatory and neurodegenerative diseases
Voet, S., Srinivasan, S., Lamkanfi, M., & van Loo, G. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810248 · Cited by 761
Self-citationSamir, P., Malireddi, R. K. S., & Kanneganti, T.-D. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00238 · Cited by 557
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Metadata
- Authors
- Van Opdenbosch, N., Gurung, P., Vande Walle, L., Fossoul, A., Kanneganti, T.-D., & Lamkanfi, M.
- Venue
- Nature Communications
- Published
- 2014-02-04
- Volume
- 5
- Issue
- 1
- Pages
- 3209-3209
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2019407752
- Cited by
- 236
- References
- 6
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
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