Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway.
Animals
COVID-19
/ immunology
Caspase 8
/ genetics
Cells, Cultured
Cytotoxicity, Immunologic
Humans
Interferon-gamma
/ genetics
Lymphohistiocytosis, Hemophagocytic
/ immunology
Macrophage Activation
Macrophages
/ immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
/ metabolism
Nitric Oxide Synthase Type II
/ metabolism
Pathogen-Associated Molecular Pattern Molecules
/ immunology
SARS-CoV-2
/ physiology
Signal Transduction
bcl-2 Homologous Antagonist-Killer Protein
/ genetics
bcl-2-Associated X Protein
/ genetics
BAX and BAK
COVID-19
SARS-CoV-2
TNF
Toll-like receptor
apoptosis
caspase-8
hemophagocytic lymphohistiocytosis
iNOS
interferon
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
21
09
2021
revised:
19
11
2021
accepted:
05
01
2022
pubmed:
10
2
2022
medline:
15
3
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35139355
pii: S1074-7613(22)00032-2
doi: 10.1016/j.immuni.2022.01.003
pmc: PMC8822620
pii:
doi:
Substances chimiques
Pathogen-Associated Molecular Pattern Molecules
0
bcl-2 Homologous Antagonist-Killer Protein
0
bcl-2-Associated X Protein
0
Interferon-gamma
82115-62-6
Nitric Oxide Synthase Type II
EC 1.14.13.39
Caspase 8
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
423-441.e9Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare that D.S.S., J.P., A.W., I.Y.K., M.R., J.P.C., K.C.D., S.H., H.A., M.D., Y.D., L.M., M.D., A.S.H., S.E.N., J.R.G., M.J.H., E.D.H., A.S., J.S., M.P., R.F., and J.E.V. are employees or former employees of the Walter and Eliza Hall Medical Institute, which receives milestone payments from Genentech and AbbVie for the development of ABT-199 for cancer therapy. J.E.V. sits on the advisory board of Avammune Therapeutics.
Références
PLoS Pathog. 2018 Sep 27;14(9):e1007299
pubmed: 30261081
Nat Rev Immunol. 2017 Mar;17(3):151-164
pubmed: 28138137
Cell Chem Biol. 2017 Apr 20;24(4):507-514.e4
pubmed: 28392147
Stem Cells. 2002;20(3):241-8
pubmed: 12004082
N Engl J Med. 2020 May 7;382(19):1811-1822
pubmed: 32374962
Cell Death Dis. 2016 Sep 01;7(9):e2348
pubmed: 27584786
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11272-7
pubmed: 16055554
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
PLoS One. 2009 Sep 21;4(9):e7059
pubmed: 19768117
Sci Transl Med. 2016 May 18;8(339):339ra69
pubmed: 27194727
Nature. 2019 Oct;574(7778):428-431
pubmed: 31511692
Immunol Rev. 2008 Dec;226:41-56
pubmed: 19161415
Cancer Cell. 2006 Nov;10(5):389-99
pubmed: 17097561
Nat Rev Mol Cell Biol. 2014 Jan;15(1):49-63
pubmed: 24355989
Nat Microbiol. 2016 Feb 24;1:15034
pubmed: 27572165
Nat Med. 2013 Feb;19(2):202-8
pubmed: 23291630
Nature. 2006 Mar 9;440(7081):237-41
pubmed: 16407889
Clin Transl Immunology. 2017 Jan 06;6(1):e124
pubmed: 28197335
Cell. 2014 May 22;157(5):1175-88
pubmed: 24813849
Genes Dev. 2005 Jun 1;19(11):1294-305
pubmed: 15901672
J Neurosci. 2002 May 15;22(10):3987-93
pubmed: 12019318
Neurology. 2004 Feb 24;62(4):635-6
pubmed: 14981185
Immunity. 2013 Sep 19;39(3):443-53
pubmed: 24012422
Cell. 2007 Apr 20;129(2):423-33
pubmed: 17448999
Cell. 2010 Mar 19;140(6):805-20
pubmed: 20303872
J Invest Dermatol. 2018 Aug;138(8):1785-1794
pubmed: 29526761
J Cell Biol. 2004 Aug 2;166(3):369-80
pubmed: 15289496
Cell Rep. 2017 Jul 18;20(3):668-682
pubmed: 28723569
Cell Cycle. 2007 Jul 15;6(14):1772-8
pubmed: 17622798
J Immunol. 2014 Feb 15;192(4):1835-46
pubmed: 24453255
Mol Pharmacol. 2008 Mar;73(3):738-47
pubmed: 18079278
Nature. 2020 Nov;587(7833):275-280
pubmed: 32971525
Cell Death Differ. 2003 Apr;10(4):418-30
pubmed: 12719719
Cell Death Differ. 2003 Jul;10(7):853-5
pubmed: 12815469
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10688-92
pubmed: 7479866
J Immunol. 2004 May 15;172(10):6272-80
pubmed: 15128816
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
J Immunol. 1999 Nov 1;163(9):4909-16
pubmed: 10528193
J Immunol. 2002 Oct 1;169(7):3900-7
pubmed: 12244188
Apoptosis. 2015 Apr;20(4):491-9
pubmed: 25578648
Cancer Res. 1998 Jul 1;58(13):2832-7
pubmed: 9661898
Infect Immun. 2013 Dec;81(12):4341-9
pubmed: 24042117
Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2200-2209
pubmed: 30674681
Infect Immun. 2014 Mar;82(3):1287-95
pubmed: 24379293
Mol Cell. 2017 Feb 16;65(4):715-729.e5
pubmed: 28212752
Cell Rep. 2018 Nov 27;25(9):2354-2368.e5
pubmed: 30485805
Clin Transl Gastroenterol. 2014 Jan 16;5:e46
pubmed: 24430113
Immunity. 2016 Sep 20;45(3):513-526
pubmed: 27523270
Immunohorizons. 2018 Jan 1;2(1):27-37
pubmed: 30467554
Cell Death Dis. 2014 Dec 04;5:e1553
pubmed: 25476901
Eur J Immunol. 2007 Dec;37(12):3311-8
pubmed: 18034428
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10845-50
pubmed: 11526215
Gastroenterology. 2011 Jun;140(7):2009-18, 2018.e1-4
pubmed: 21354149
Nat Immunol. 2016 Jan;17(1):34-40
pubmed: 26681460
Mol Cell. 2017 Jun 1;66(5):698-710.e5
pubmed: 28506461
PLoS Pathog. 2016 Oct 13;12(10):e1005910
pubmed: 27737018
PLoS One. 2011 May 02;6(5):e19105
pubmed: 21559306
Cell Cycle. 2014;13(12):1948-57
pubmed: 24762656
Nat Commun. 2019 May 17;10(1):2201
pubmed: 31101814
J Cell Biol. 2004 Jun 21;165(6):835-42
pubmed: 15210730
Cell. 2007 Nov 16;131(4):682-93
pubmed: 18022363
Sci Rep. 2019 Feb 26;9(1):2788
pubmed: 30808944
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Cell Rep. 2018 Nov 27;25(9):2339-2353.e4
pubmed: 30485804
J Cell Biol. 2004 Jun 21;165(6):775-80
pubmed: 15210727
Nature. 2019 Nov;575(7784):683-687
pubmed: 31748744
Nat Commun. 2015 Feb 18;6:6282
pubmed: 25693118
Cell Microbiol. 2016 Apr;18(4):466-74
pubmed: 26833712
Immunity. 2020 Sep 15;53(3):533-547.e7
pubmed: 32735843
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Cancer Res. 2018 Apr 15;78(8):1948-1957
pubmed: 29431638
Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11926-11935
pubmed: 31147458
Nat Commun. 2015 Jun 24;6:7515
pubmed: 26104484
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Cell Death Differ. 2017 Mar;24(3):481-491
pubmed: 28106882
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
J Immunol. 1998 Mar 15;160(6):2590-6
pubmed: 9510156
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
Methods Mol Biol. 2018;1784:35-49
pubmed: 29761386
J Immunol. 1998 Jan 15;160(2):943-52
pubmed: 9551933
Biochim Biophys Acta. 1999 May 5;1411(2-3):401-14
pubmed: 10320672
Elife. 2014 Dec 02;3:
pubmed: 25443632
Mol Cell Biol. 2004 Feb;24(4):1464-9
pubmed: 14749364
N Engl J Med. 2020 Jan 30;382(5):437-445
pubmed: 31995689
Cell. 1995 Feb 10;80(3):401-11
pubmed: 7859282
Immunity. 2009 Oct 16;31(4):539-50
pubmed: 19833085
J Leukoc Biol. 2020 Feb;107(2):273-284
pubmed: 31793076
Immunity. 2012 Feb 24;36(2):215-27
pubmed: 22365665
Mol Cell Biol. 1997 Sep;17(9):5328-37
pubmed: 9271410
Nucleic Acids Res. 2018 Jan 4;46(D1):D380-D386
pubmed: 29087512
Nature. 2015 Oct 29;526(7575):666-71
pubmed: 26375259
J Immunol. 2012 Dec 15;189(12):5508-12
pubmed: 23144495
Nat Rev Immunol. 2014 Jan;14(1):51-9
pubmed: 24336099
J Clin Invest. 2016 Nov 1;126(11):4346-4360
pubmed: 27756058
Genes Dev. 1995 Aug 15;9(16):1965-77
pubmed: 7649478
Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20054-9
pubmed: 22123964
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Nature. 2021 Mar;591(7848):131-136
pubmed: 33472215
Science. 2003 Nov 7;302(5647):1036-8
pubmed: 14500851
Nature. 1994 Dec 8;372(6506):560-3
pubmed: 7990930
J Infect Dis. 1993 Jun;167(6):1358-63
pubmed: 7684756
J Immunol. 2003 Aug 15;171(4):2042-9
pubmed: 12902509
Nature. 2015 Oct 29;526(7575):660-5
pubmed: 26375003
J Immunol. 1999 Jul 15;163(2):920-6
pubmed: 10395688
Immunity. 2021 Jul 13;54(7):1447-1462.e5
pubmed: 33979579
J Immunol. 2014 Mar 1;192(5):2326-38
pubmed: 24477906
Nat Commun. 2019 Apr 3;10(1):1523
pubmed: 30944313
Eur J Immunol. 1997 Oct;27(10):2600-9
pubmed: 9368616
J Exp Med. 2002 Jan 21;195(2):161-9
pubmed: 11805143
Nature. 2002 Oct 10;419(6907):634-7
pubmed: 12374983
Nat Rev Immunol. 2018 Sep;18(9):545-558
pubmed: 29921905
Nat Commun. 2020 Jun 19;11(1):3150
pubmed: 32561755
J Biol Chem. 2005 Dec 9;280(49):40599-608
pubmed: 16227629
Sci Rep. 2017 May 22;7(1):2244
pubmed: 28533524
EMBO Rep. 2014 Sep;15(9):982-90
pubmed: 24990442
Signal Transduct Target Ther. 2020 Oct 9;5(1):235
pubmed: 33037188
Nat Commun. 2018 Sep 25;9(1):3910
pubmed: 30254289
Nature. 2013 Apr 25;496(7446):445-55
pubmed: 23619691
Methods Mol Biol. 2018;1714:41-55
pubmed: 29177854
Mol Cell Biol. 2011 Jul;31(14):2934-46
pubmed: 21576359
Cell. 2021 Jan 7;184(1):149-168.e17
pubmed: 33278357
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Nature. 2020 Jan;577(7788):103-108
pubmed: 31827281
Nat Immunol. 2015 Aug;16(8):838-849
pubmed: 26147685
Cell Rep. 2020 Mar 31;30(13):4343-4354.e4
pubmed: 32234472
Immunobiology. 2006;211(6-8):511-24
pubmed: 16920490
Stem Cell Res Ther. 2019 Jan 11;10(1):18
pubmed: 30635041
Nature. 2019 Nov;575(7784):679-682
pubmed: 31723262
Front Immunol. 2020 Aug 25;11:1840
pubmed: 32983099
Cell. 1998 Aug 21;94(4):491-501
pubmed: 9727492
J Biol Chem. 1997 Feb 21;272(8):4959-63
pubmed: 9030556
Curr Opin Immunol. 2021 Feb;68:83-97
pubmed: 33160107
Immunity. 2016 Jul 19;45(1):46-59
pubmed: 27396959