Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4
- Author
- Nina Van Opdenbosch (UGent) , Hanne Van Gorp (UGent) , Maarten Verdonckt (UGent) , Pedro Henrique Viana Saavedra (UGent) , Nathalia Moraes de Vasconcelos (UGent) , Amanda Gonçalves (UGent) , Lieselotte Vande Walle (UGent) , Dieter Demon (UGent) , Magdalena Matusiak (UGent) , Filip Van Hauwermeiren (UGent) , Jinke D'Hont (UGent) , Tino Hochepied (UGent) , Stefan Krautwald, Thirumala-Devi Kanneganti and Mohamed Lamkanfi (UGent)
- Organization
- Abstract
- The caspase activation and recruitment domain (CARD)-based inflammasome sensors NLRP1b and NLRC4 induce caspase-1-dependent pyroptosis independent of the inflammasome adaptor ASC. Here, we show that NLRP1b and NLRC4 trigger caspase-8-mediated apoptosis as an alternative cell death program in caspase-1(-/-) macrophages and intestinal epithelial organoids (IECs). The caspase-8 adaptor FADD was recruited to ASC specks, which served as cytosolic platforms for caspase-8 activation and NLRP1b/NLRC4-induced apoptosis. We further found that caspase-1 protease activity dominated over scaffolding functions in suppressing caspase-8 activation and induction of apoptosis of macrophages and IECs. Moreover, TLR-induced c-FLIP expression inhibited caspase-8-mediated apoptosis downstream of ASC speck assembly, but did not affect pyroptosis induction by NLRP1b and NLRC4. Moreover, unlike during pyroptosis, NLRP1b- and NLRC4-elicited apoptosis retained alarmins and the inflammasome-matured cytokines interleukin 1 beta (IL-1 beta) and IL-18 intracellularly. This work identifies critical mechanisms regulating apoptosis induction by the inflammasome sensors NLRP1b and NLRC4 and suggests converting pyroptosis into apoptosis as a paradigm for suppressing inflammation.
- Keywords
- ANTHRAX LETHAL TOXIN, PYROPTOTIC CELL-DEATH, CAUSES AUTOINFLAMMATION, SALMONELLA INFECTION, PYRIN INFLAMMASOME, ACTIVATION, INTERLEUKIN-1-BETA, IL-1-BETA, INDUCTION, BACTERIAL
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8543735
- MLA
- Van Opdenbosch, Nina, et al. “Caspase-1 Engagement and TLR-Induced c-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors NLRP1b and NLRC4.” CELL REPORTS, vol. 21, no. 12, 2017, pp. 3427–44, doi:10.1016/j.celrep.2017.11.088.
- APA
- Van Opdenbosch, N., Van Gorp, H., Verdonckt, M., Viana Saavedra, P. H., Moraes de Vasconcelos, N., Gonçalves, A., … Lamkanfi, M. (2017). Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4. CELL REPORTS, 21(12), 3427–3444. https://doi.org/10.1016/j.celrep.2017.11.088
- Chicago author-date
- Van Opdenbosch, Nina, Hanne Van Gorp, Maarten Verdonckt, Pedro Henrique Viana Saavedra, Nathalia Moraes de Vasconcelos, Amanda Gonçalves, Lieselotte Vande Walle, et al. 2017. “Caspase-1 Engagement and TLR-Induced c-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors NLRP1b and NLRC4.” CELL REPORTS 21 (12): 3427–44. https://doi.org/10.1016/j.celrep.2017.11.088.
- Chicago author-date (all authors)
- Van Opdenbosch, Nina, Hanne Van Gorp, Maarten Verdonckt, Pedro Henrique Viana Saavedra, Nathalia Moraes de Vasconcelos, Amanda Gonçalves, Lieselotte Vande Walle, Dieter Demon, Magdalena Matusiak, Filip Van Hauwermeiren, Jinke D’Hont, Tino Hochepied, Stefan Krautwald, Thirumala-Devi Kanneganti, and Mohamed Lamkanfi. 2017. “Caspase-1 Engagement and TLR-Induced c-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors NLRP1b and NLRC4.” CELL REPORTS 21 (12): 3427–3444. doi:10.1016/j.celrep.2017.11.088.
- Vancouver
- 1.Van Opdenbosch N, Van Gorp H, Verdonckt M, Viana Saavedra PH, Moraes de Vasconcelos N, Gonçalves A, et al. Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4. CELL REPORTS. 2017;21(12):3427–44.
- IEEE
- [1]N. Van Opdenbosch et al., “Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4,” CELL REPORTS, vol. 21, no. 12, pp. 3427–3444, 2017.
@article{8543735,
abstract = {{The caspase activation and recruitment domain (CARD)-based inflammasome sensors NLRP1b and NLRC4 induce caspase-1-dependent pyroptosis independent of the inflammasome adaptor ASC. Here, we show that NLRP1b and NLRC4 trigger caspase-8-mediated apoptosis as an alternative cell death program in caspase-1(-/-) macrophages and intestinal epithelial organoids (IECs). The caspase-8 adaptor FADD was recruited to ASC specks, which served as cytosolic platforms for caspase-8 activation and NLRP1b/NLRC4-induced apoptosis. We further found that caspase-1 protease activity dominated over scaffolding functions in suppressing caspase-8 activation and induction of apoptosis of macrophages and IECs. Moreover, TLR-induced c-FLIP expression inhibited caspase-8-mediated apoptosis downstream of ASC speck assembly, but did not affect pyroptosis induction by NLRP1b and NLRC4. Moreover, unlike during pyroptosis, NLRP1b- and NLRC4-elicited apoptosis retained alarmins and the inflammasome-matured cytokines interleukin 1 beta (IL-1 beta) and IL-18 intracellularly. This work identifies critical mechanisms regulating apoptosis induction by the inflammasome sensors NLRP1b and NLRC4 and suggests converting pyroptosis into apoptosis as a paradigm for suppressing inflammation.}},
author = {{Van Opdenbosch, Nina and Van Gorp, Hanne and Verdonckt, Maarten and Viana Saavedra, Pedro Henrique and Moraes de Vasconcelos, Nathalia and Gonçalves, Amanda and Vande Walle, Lieselotte and Demon, Dieter and Matusiak, Magdalena and Van Hauwermeiren, Filip and D'Hont, Jinke and Hochepied, Tino and Krautwald, Stefan and Kanneganti, Thirumala-Devi and Lamkanfi, Mohamed}},
issn = {{2211-1247}},
journal = {{CELL REPORTS}},
keywords = {{ANTHRAX LETHAL TOXIN,PYROPTOTIC CELL-DEATH,CAUSES AUTOINFLAMMATION,SALMONELLA INFECTION,PYRIN INFLAMMASOME,ACTIVATION,INTERLEUKIN-1-BETA,IL-1-BETA,INDUCTION,BACTERIAL}},
language = {{eng}},
number = {{12}},
pages = {{3427--3444}},
title = {{Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4}},
url = {{http://doi.org/10.1016/j.celrep.2017.11.088}},
volume = {{21}},
year = {{2017}},
}
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