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Caspase-1 Engagement and TLR-Induced c-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors NLRP1b and NLRC4.
Van Opdenbosch, Nina; Van Gorp, Hanne; Verdonckt, Maarten; Saavedra, Pedro H V; de Vasconcelos, Nathalia M; Gonçalves, Amanda; Vande Walle, Lieselotte; Demon, Dieter; Matusiak, Magdalena; Van Hauwermeiren, Filip; D'Hont, Jinke; Hochepied, Tino; Krautwald, Stefan; Kanneganti, Thirumala-Devi; Lamkanfi, Mohamed.
Afiliación
  • Van Opdenbosch N; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Van Gorp H; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Verdonckt M; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Saavedra PHV; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • de Vasconcelos NM; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Gonçalves A; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium; VIB Bioimaging Core, VIB, 9000 Ghent, Belgium.
  • Vande Walle L; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Demon D; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Matusiak M; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • Van Hauwermeiren F; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium.
  • D'Hont J; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
  • Hochepied T; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
  • Krautwald S; Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
  • Kanneganti TD; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
  • Lamkanfi M; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium; VIB-UGent Center for Inflammation Research, VIB, 9052 Ghent, Belgium. Electronic address: mohamed.lamkanfi@irc.vib-ugent.be.
Cell Rep ; 21(12): 3427-3444, 2017 Dec 19.
Article en En | MEDLINE | ID: mdl-29262324
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 1ß (IL-1ß) 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Caspasa 1 / Proteínas Reguladoras de la Apoptosis / Proteína Reguladora de Apoptosis Similar a CASP8 y FADD / Inflamasomas / Piroptosis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Caspasa 1 / Proteínas Reguladoras de la Apoptosis / Proteína Reguladora de Apoptosis Similar a CASP8 y FADD / Inflamasomas / Piroptosis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos