Activation of the NLRP1B inflammasome by caspase-8.

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Caspase 8*/metabolism ; Caspase 8*/genetics ; Inflammasomes*/metabolism ; Macrophages*/metabolism ; Apoptosis Regulatory Proteins*/metabolism ; Apoptosis Regulatory Proteins*/genetics; Animals ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Toll-Like Receptor 4/metabolism ; Caspase 1/metabolism ; Humans ; Mice, Knockout ; Apoptosis

Cleavage of the innate immune receptor NLRP1B by various microbial proteases causes the proteasomal degradation of its N-terminal fragment and the subsequent release of a C-terminal fragment that forms an inflammasome. We reported previously that metabolic stress caused by intracellular bacteria triggers NLRP1B activation, but the mechanism by which this occurs was not elucidated. Here we demonstrate that TLR4 signaling in metabolically stressed macrophages promotes the formation of a TRIF/RIPK1/caspase-8 complex. Caspase-8 activity, induced downstream of this TLR4 pathway or through a distinct TNF receptor pathway, causes cleavage and activation of NLRP1B, which facilitates the maturation of both pro-caspase-1 and pro-caspase-8. Thus, our findings indicate that caspase-8 and NLRP1B generate a positive feedback loop that amplifies cell death processes and promotes a pro-inflammatory response through caspase-1. The ability of NLRP1B to detect caspase-8 activity suggests that this pattern recognition receptor may play a role in the defense against a variety of pathogens that induce apoptosis.
(© 2024. The Author(s).)

Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12710-5. (PMID: 22802624)
Elife. 2021 Jan 07;10:. (PMID: 33410748)
Science. 1997 Oct 31;278(5339):860-6. (PMID: 9346484)
J Biol Chem. 2018 Dec 7;293(49):18864-18878. (PMID: 30291141)
Infect Immun. 2014 Sep;82(9):3697-703. (PMID: 24935976)
Nature. 2021 Apr;592(7856):773-777. (PMID: 33731929)
J Mol Biol. 2003 Feb 7;326(1):105-15. (PMID: 12547194)
Science. 2021 Jan 29;371(6528):. (PMID: 33243852)
J Biol Chem. 1999 Oct 22;274(43):30353-6. (PMID: 10521409)
Cell Rep. 2023 Jan 31;42(1):111966. (PMID: 36649710)
J Immunol. 2019 Aug 15;203(4):783-788. (PMID: 31243089)
Cold Spring Harb Perspect Biol. 2020 Mar 2;12(3):. (PMID: 31427374)
Cell Microbiol. 2005 Feb;7(2):281-92. (PMID: 15659071)
Nature. 2010 Oct 14;467(7317):863-7. (PMID: 20944749)
Nature. 2021 Apr;592(7856):778-783. (PMID: 33731932)
Front Immunol. 2022 Dec 01;13:1067164. (PMID: 36532075)
Cell Death Differ. 2013 Sep;20(9):1149-60. (PMID: 23645208)
Nat Cell Biol. 2017 Oct;19(10):1237-1247. (PMID: 28920952)
Infect Immun. 2017 Oct 18;85(11):. (PMID: 28808162)
Nat Immunol. 2022 Jun;23(6):916-926. (PMID: 35618833)
PLoS One. 2011;6(11):e27396. (PMID: 22087307)
Infect Immun. 2013 Feb;81(2):570-9. (PMID: 23230290)
Cell Rep. 2018 Aug 7;24(6):1425-1433. (PMID: 30089254)
Infect Immun. 1982 Mar;35(3):852-60. (PMID: 6279518)
J Biol Chem. 2003 Dec 12;278(50):49751-62. (PMID: 14519765)
Sci Signal. 2016 Aug 23;9(442):ra85. (PMID: 27555662)
Curr Opin Cell Biol. 2020 Apr;63:186-193. (PMID: 32163825)
Nat Commun. 2024 Jan 2;15(1):130. (PMID: 38167258)
Immunity. 2013 Jun 27;38(6):1142-53. (PMID: 23809161)
Science. 1999 Apr 9;284(5412):309-13. (PMID: 10195894)
Nat Immunol. 2010 May;11(5):373-84. (PMID: 20404851)
Nat Commun. 2019 Apr 15;10(1):1729. (PMID: 30988283)
J Exp Med. 2023 Jan 2;220(1):. (PMID: 36315050)
Nature. 2014 Mar 20;507(7492):329-34. (PMID: 24646995)
Cell Rep. 2017 Dec 19;21(12):3427-3444. (PMID: 29262324)
Immunity. 2019 Oct 15;51(4):609-624. (PMID: 31473100)
Mol Cell. 2022 Jul 7;82(13):2385-2400.e9. (PMID: 35594856)
Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10888-E10897. (PMID: 30381458)
Mol Cell. 2017 Jun 1;66(5):698-710.e5. (PMID: 28506461)
Science. 2018 Nov 30;362(6418):1064-1069. (PMID: 30361383)
Infect Immun. 1986 Feb;51(2):461-9. (PMID: 3510976)
Curr Opin Microbiol. 2020 Apr;54:111-118. (PMID: 32092691)
Science. 2022 Jul 15;377(6603):328-335. (PMID: 35857590)
Cell Death Differ. 2022 Jan;29(1):147-155. (PMID: 34354257)
Nat Immunol. 2008 Apr;9(4):361-8. (PMID: 18297073)
Nat Commun. 2017 Aug 25;8(1):359. (PMID: 28842570)
Mol Cell. 2015 Oct 1;60(1):63-76. (PMID: 26344099)
Cell Host Microbe. 2012 Apr 19;11(4):337-51. (PMID: 22520462)
J Immunol. 2013 Nov 15;191(10):5239-46. (PMID: 24123685)
Science. 2020 Dec 4;370(6521):. (PMID: 33093214)
J Biol Chem. 2012 Jul 20;287(30):25030-7. (PMID: 22665479)
Nat Rev Immunol. 2023 Oct;23(10):635-654. (PMID: 36973360)
Nat Cell Biol. 2018 Dec;20(12):1389-1399. (PMID: 30420664)
Nature. 2015 Oct 29;526(7575):666-71. (PMID: 26375259)
Nat Cell Biol. 2017 Oct;19(10):1248-1259. (PMID: 28920954)
Cell. 2018 May 17;173(5):1244-1253.e10. (PMID: 29681455)
Science. 2019 Apr 5;364(6435):. (PMID: 30872533)
Cell. 1997 Oct 17;91(2):243-52. (PMID: 9346241)
Science. 2019 Apr 5;364(6435):82-85. (PMID: 30872531)
PLoS Pathog. 2012;8(4):e1002659. (PMID: 22536155)
Immunol Rev. 2017 May;277(1):76-89. (PMID: 28462525)
Science. 2013 Feb 15;339(6121):819-23. (PMID: 23287718)
Cold Spring Harb Perspect Biol. 2020 May 1;12(5):. (PMID: 31570336)
Nat Rev Immunol. 2016 Jul;16(7):407-20. (PMID: 27291964)
J Biol Chem. 2000 Aug 25;275(34):25883-91. (PMID: 10823818)
Cell Death Differ. 2017 Aug;24(8):1380-1389. (PMID: 28498362)

EC 3.4.22.- (Caspase 8)
0 (Inflammasomes)
0 (Nalp1b protein, mouse)
0 (Apoptosis Regulatory Proteins)
EC 3.4.22.- (Casp8 protein, mouse)
0 (Toll-Like Receptor 4)
EC 3.4.22.36 (Caspase 1)
0 (Tlr4 protein, mouse)

Date Created: 20240917 Date Completed: 20240917 Latest Revision: 20240920

20240920

PMC11408587

10.1038/s42003-024-06882-3

39289441