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Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway.
Simpson, Daniel S; Pang, Jiyi; Weir, Ashley; Kong, Isabella Y; Fritsch, Melanie; Rashidi, Maryam; Cooney, James P; Davidson, Kathryn C; Speir, Mary; Djajawi, Tirta M; Hughes, Sebastian; Mackiewicz, Liana; Dayton, Merle; Anderton, Holly; Doerflinger, Marcel; Deng, Yexuan; Huang, Allan Shuai; Conos, Stephanie A; Tye, Hazel; Chow, Seong H; Rahman, Arfatur; Norton, Raymond S; Naderer, Thomas; Nicholson, Sandra E; Burgio, Gaetan; Man, Si Ming; Groom, Joanna R; Herold, Marco J; Hawkins, Edwin D; Lawlor, Kate E; Strasser, Andreas; Silke, John; Pellegrini, Marc; Kashkar, Hamid; Feltham, Rebecca; Vince, James E.
Afiliación
  • Simpson DS; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Pang J; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia; College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • Weir A; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Kong IY; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Fritsch M; Institute for Molecular Immunology, Centre for Molecular Medicine Cologne and Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases, University of Cologne, Cologne, 50931, Germany.
  • Rashidi M; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Cooney JP; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Davidson KC; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Speir M; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia.
  • Djajawi TM; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia.
  • Hughes S; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Mackiewicz L; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
  • Dayton M; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
  • Anderton H; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Doerflinger M; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Deng Y; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Huang AS; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Conos SA; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia.
  • Tye H; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia.
  • Chow SH; The Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Rahman A; Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Norton RS; Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia; ARC Centre for Fragment-Based Design, Monash University, Parkville, VIC, 3052, Australia.
  • Naderer T; The Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Nicholson SE; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Burgio G; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
  • Man SM; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
  • Groom JR; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Herold MJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Hawkins ED; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Lawlor KE; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia.
  • Strasser A; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Silke J; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Pellegrini M; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
  • Kashkar H; Institute for Molecular Immunology, Centre for Molecular Medicine Cologne and Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases, University of Cologne, Cologne, 50931, Germany.
  • Feltham R; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: feltham.r@wehi.edu.au.
  • Vince JE; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: vince@wehi.edu.au.
Immunity ; 55(3): 423-441.e9, 2022 03 08.
Article en En | MEDLINE | ID: mdl-35139355
ABSTRACT
Cell death plays an important role during pathogen infections. Here, we report that interferon-γ (IFNγ) sensitizes macrophages to Toll-like receptor (TLR)-induced death that requires macrophage-intrinsic death ligands and caspase-8 enzymatic activity, which trigger the mitochondrial apoptotic effectors, BAX and BAK. The pro-apoptotic caspase-8 substrate BID was dispensable for BAX and BAK activation. Instead, caspase-8 reduced pro-survival BCL-2 transcription and increased inducible nitric oxide synthase (iNOS), thus facilitating BAX and BAK signaling. IFNγ-primed, TLR-induced macrophage killing required iNOS, which licensed apoptotic caspase-8 activity and reduced the BAX and BAK inhibitors, A1 and MCL-1. The deletion of iNOS or caspase-8 limited SARS-CoV-2-induced disease in mice, while caspase-8 caused lethality independent of iNOS in a model of hemophagocytic lymphohistiocytosis. These findings reveal that iNOS selectively licenses programmed cell death, which may explain how nitric oxide impacts disease severity in SARS-CoV-2 infection and other iNOS-associated inflammatory conditions.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Interferón gamma / Linfohistiocitosis Hemofagocítica / Caspasa 8 / SARS-CoV-2 / COVID-19 / Macrófagos / Mitocondrias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Australia
Texto completo
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XML
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Interferón gamma / Linfohistiocitosis Hemofagocítica / Caspasa 8 / SARS-CoV-2 / COVID-19 / Macrófagos / Mitocondrias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Australia