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What Is the Pathobiology of Inflammation to Cell Death? Apoptosis, Necrosis, Necroptosis, Autophagic Cell Death, Pyroptosis, and NETosis

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Autophagy Networks in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Cell death and immunity are two evolutionarily-conserved processes that maintain homeostasis under changing conditions in the internal and external environment. Although these processes utilize fundamentally different machinery, cell death and immunity are highly interconnected and share a number of critical modifiers. Inflammation, the body’s important immune response to injuries or infections, is a complex process involving various types of immune cells and signaling molecules. Different types of cell death including apoptosis, necrosis, necroptosis, autophagic cell death, pyroptosis, and NETosis can lead to the development of different immune and inflammatory responses including either immunogenic cell death (ICD) or tolerogenic cell death (TCD). The molecular mechanisms of ICD and TCD are beginning to be elucidated and have critical implications for the treatment of various acute and chronic diseases. In particular, damage-associated molecular patterns (DAMPs), endogenous molecules released during cell death and tissue injury, exhibit cytokine and chemokine activities in the regulation of the balance between ICD and TCD. In this chapter, recent advances in our understanding of the relationship between cell death, inflammation, and DAMPs are reviewed.

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Abbreviations

ACD:

Accidental cell death

AIF:

Apoptosis-inducing factor

AIM2:

Absent in melanoma 2

ASC:

Apoptosis-associated speck-like protein containing a CARD

ATG:

Autophagy-related

ATP:

Adenosine triphosphate

Bak:

Bcl-2 homologous antagonist/killer

Bax:

bcl-2-like protein 4

BCL10:

B-cell CLL/lymphoma 10

Bcl-2:

B-cell lymphoma 2

Bcl-xL:

B-cell lymphoma-extra large

BECN1:

Beclin 1

Bid:

BH3 interacting-domain death agonist

CTLs:

Cytotoxic T lymphocytes

DAMPs:

Damage-associated molecular patterns

DCC:

Colorectal carcinoma

DRs:

Death receptors

ENDOG:

Endonuclease G

FADD:

Fas-Associated protein with Death Domain

HMGB1:

High mobility group box 1

HSPs:

Heat shock proteins

IBD:

Inflammatory bowel disease

ICD:

Immunogenic cell death

IFN:

Interferon

IL:

Interleukin

LAMP:

Lysosomal-associated membrane protein

LAP:

LC3-associated phagocytosis

LC3:

Microtubule-associated protein 1 light chain 3

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinases

MDA5:

Melanoma differentiation-associated protein 5

MLKL:

Mixed lineage kinase domain-like protein

MPO:

Myeloperoxidase

NADPH:

Nicotinamide adenine dinucleotide phosphate-oxidase

NCCD:

Nomenclature Committee on Cell Death

NDP52/CALCOCO2:

Nuclear dot protein 52

NETs:

Neutrophil extracellular traps

NF-κB:

Nuclear factor-κB

NK:

Natural killer

NLRC4:

NLR family CARD domain-containing protein 4

NLRP1:

NLR family pyrin domain containing 1

NLRs:

NOD-like receptors

Omi/HTRA2:

HtrA serine peptidase 2

PAMPs:

Pathogen-associated molecular patterns

PARP-1:

Poly ADP-ribose polymerase 1

PD4:

Peptidylarginine deiminase 4

PIK3C3:

Phosphatidylinositol 3-kinase, catalytic subunit type 3

PIK3R4:

Phosphoinositide-3-kinase, regulatory subunit 4

PKB/AKT:

Protein kinase B

PMA:

Phorbol myristate acetate

PRRs:

Pattern recognition receptors

PtdIns3K:

Phosphatidylinositol 3-kinase

PUMA:

p53 upregulated modulator of apoptosis

RAGE:

The receptor for advanced glycation end products

RB1CC1/FIP200:

RB1-Inducible Coiled-Coil 1/FAK Family Kinase-Interacting Protein of 200 kDa

RCD:

Regulated cell death

RIG-1:

Retinoic acid-inducible gene 1

RIP3/RIPK3:

Receptor-interacting serine-threonine kinase 3

RLRs:

RIG-I-like receptors

ROS:

Reactive oxygen species

SMAC/DIABLO:

Second mitochondria-derived activator of caspases

SQSTM1/p62:

Sequestosome 1

STAT3:

Signal transducer and activator of transcription 3

T3SS:

Type III secretion system

TAX1BP1:

Human T-cell leukemia virus type I binding protein 1

TCD:

Tolerogenic cell death

TIM3:

T-cell immunoglobulin mucin 3

TLRs:

Toll-like receptors

TMEM173/STING:

Transmembrane protein 173

TNF:

Tumor necrosis factor

TNFR1:

TNF receptor 1

TRAIL:

TNF-related apoptosis-inducing ligand

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

ULK1:

UNC-51-like kinase 1

UNC5A:

unc-5 homolog A

VPS34:

Vacuolar protein sorting 34

WIPI1:

WD repeat domain phosphoinositide-interacting protein 1

ZBP1/DAI:

Z-DNA-binding protein 1.

References

  1. Abnave P, Mottola G, Gimenez G et al (2014) Screening in planarians identifies MORN2 as a key component in LC3-associated phagocytosis and resistance to bacterial infection. Cell Host Microbe 16:338–350

    Article  CAS  PubMed  Google Scholar 

  2. Akira S, Hemmi H (2003) Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett 85:85–95

    Article  CAS  PubMed  Google Scholar 

  3. Alexander DE, Leib DA (2008) Xenophagy in herpes simplex virus replication and pathogenesis. Autophagy 4:101–103

    Article  PubMed  Google Scholar 

  4. Allam R, Darisipudi MN, Tschopp J et al (2013) Histones trigger sterile inflammation by activating the NLRP3 inflammasome. Eur J Immunol 43:3336–3342

    Article  CAS  PubMed  Google Scholar 

  5. Allam R, Kumar SV, Darisipudi MN et al (2014) Extracellular histones in tissue injury and inflammation. J Mol Med 92:465–472

    Article  CAS  PubMed  Google Scholar 

  6. Andersson U, Tracey KJ (2011) HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 29:139–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059

    Article  CAS  PubMed  Google Scholar 

  8. Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260

    Article  CAS  PubMed  Google Scholar 

  9. Behrends C, Sowa ME, Gygi SP et al (2010) Network organization of the human autophagy system. Nature 466:68–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bell CW, Jiang W, Reich CF 3rd et al (2006) The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 291:C1318–C1325

    Article  CAS  PubMed  Google Scholar 

  11. Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7:99–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5

    Article  CAS  PubMed  Google Scholar 

  13. Bonapace L, Bornhauser BC, Schmitz M et al (2010) Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest 120:1310–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Branzk N, Papayannopoulos V (2013) Molecular mechanisms regulating NETosis in infection and disease. Semin Immunopathol 35:513–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brennan MA, Cookson BT (2000) Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38:31–40

    Article  CAS  PubMed  Google Scholar 

  16. Brinkmann V, Reichard U, Goosmann C et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535

    Article  CAS  PubMed  Google Scholar 

  17. Cai Z, Jitkaew S, Zhao J et al (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 16:55–65

    Article  CAS  PubMed  Google Scholar 

  18. Castillo EF, Dekonenko A, Arko-Mensah J et al (2012) Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci U S A 109:E3168–E3176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cavanagh MM, Weyand CM, Goronzy JJ (2012) Chronic inflammation and aging: DNA damage tips the balance. Curr Opin Immunol 24:488–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen GY, Tang J, Zheng P et al (2009) CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323:1722–1725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen R, Kang R, Fan XG et al (2014) Release and activity of histone in diseases. Cell Death Dis 5:e1370. doi:10.1038/cddis.2014.337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cho YS, Challa S, Moquin D et al (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368:651–662

    Article  CAS  PubMed  Google Scholar 

  24. Christenson K, Thoren FB, Bylund J (2012) Analyzing cell death events in cultured leukocytes. Methods Mol Biol 844:65–86

    Article  CAS  PubMed  Google Scholar 

  25. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dannappel M, Vlantis K, Kumari S et al (2014) RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513:90–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Daugas E, Susin SA, Zamzami N et al (2000) Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J 14:729–739

    CAS  PubMed  Google Scholar 

  28. Degterev A, Huang Z, Boyce M et al (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119

    Article  CAS  PubMed  Google Scholar 

  29. Demers M, Wagner DD (2014) NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost 40:277–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deretic V (2011) Autophagy in immunity and cell-autonomous defense against intracellular microbes. Immunol Rev 240:92–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Deretic V, Levine B (2009) Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5:527–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13:722–737

    Article  CAS  PubMed  Google Scholar 

  33. Ditsworth D, Zong WX, Thompson CB (2007) Activation of poly(ADP)-ribose polymerase (PARP-1) induces release of the pro-inflammatory mediator HMGB1 from the nucleus. J Biol Chem 282:17845–17854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Du C, Fang M, Li Y et al (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    Article  CAS  PubMed  Google Scholar 

  35. Duewell P, Kono H, Rayner KJ et al (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dupont N, Jiang S, Pilli M et al (2011) Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1beta. EMBO J 30:4701–4711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Duprez L, Takahashi N, Van Hauwermeiren F et al (2011) RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35:908–918

    Article  CAS  PubMed  Google Scholar 

  38. Eder C (2009) Mechanisms of interleukin-1beta release. Immunobiology 214:543–553

    Article  CAS  PubMed  Google Scholar 

  39. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127:514–525

    Article  CAS  PubMed  Google Scholar 

  41. Feng Y, He D, Yao Z et al (2014) The machinery of macroautophagy. Cell Res 24:24–41

    Article  CAS  PubMed  Google Scholar 

  42. Flannagan RS, Jaumouille V, Grinstein S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7:61–98

    Article  CAS  PubMed  Google Scholar 

  43. Franchi L, Kamada N, Nakamura Y et al (2012) NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 13:449–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Friggeri A, Yang Y, Banerjee S et al (2010) HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin. Am J Physiol Cell Physiol 299:C1267–C1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Galluzzi L, Bravo-San Pedro JM, Vitale I et al (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22:58–73

    Article  CAS  PubMed  Google Scholar 

  46. Galluzzi L, Maiuri MC, Vitale I et al (2007) Cell death modalities: classification and pathophysiological implications. Cell Death Differ 14:1237–1243

    Article  CAS  PubMed  Google Scholar 

  47. Galluzzi L, Vitale I, Abrams JM et al (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19:107–120

    Article  CAS  PubMed  Google Scholar 

  48. Gardella S, Andrei C, Ferrera D et al (2002) The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 3:995–1001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Garg AD, Krysko DV, Vandenabeele P et al (2012) Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin. Cancer Immunol Immunother 61:215–221

    Article  CAS  PubMed  Google Scholar 

  50. Ghiringhelli F, Apetoh L, Tesniere A et al (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15:1170–1178

    Article  CAS  PubMed  Google Scholar 

  51. Goodwin GH, Sanders C, Johns EW (1973) A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem 38:14–19

    Article  CAS  PubMed  Google Scholar 

  52. Green DR, Ferguson T, Zitvogel L et al (2009) Immunogenic and tolerogenic cell death. Nat Rev Immunol 9:353–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gullstrand B, Lefort MH, Tyden H et al (2012) Combination of autoantibodies against different histone proteins influences complement-dependent phagocytosis of necrotic cell material by polymorphonuclear leukocytes in systemic lupus erythematosus. J Rheumatol 39:1619–1627

    Article  PubMed  Google Scholar 

  54. Hahn S, Giaglis S, Chowdhury CS et al (2013) Modulation of neutrophil NETosis: interplay between infectious agents and underlying host physiology. Semin Immunopathol 35:439–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Harris J, Hartman M, Roche C et al (2011) Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J Biol Chem 286:9587–9597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. He S, Wang L, Miao L et al (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137:1100–1111

    Article  CAS  PubMed  Google Scholar 

  57. Hegde R, Srinivasula SM, Zhang Z et al (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432–438

    Article  CAS  PubMed  Google Scholar 

  58. Hochreiter-Hufford A, Ravichandran KS (2013) Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol 5:a008748. doi:10.1101/cshperspect.a008748

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Hohlfeld R, Kerschensteiner M, Meinl E (2007) Dual role of inflammation in CNS disease. Neurology 68:58–63; discussion S91–S96

    Article  Google Scholar 

  60. Hoque R, Sohail M, Malik A et al (2011) TLR9 and the NLRP3 inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology 141:358–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hornung V, Ablasser A, Charrel-Dennis M et al (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hosokawa N, Hara T, Kaizuka T et al (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20:1981–1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hou W, Zhang Q, Yan Z et al (2013) Strange attractors: DAMPs and autophagy link tumor cell death and immunity. Cell Death Dis 4:e966. doi:10.1038/cddis.2013.493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Huang H, Chen HW, Evankovich J et al (2013) Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury. J Immunol 191:2665–2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang H, Evankovich J, Yan W et al (2011) Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice. Hepatology 54:999–1008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Iyer SS, Accardi CJ, Ziegler TR et al (2009) Cysteine redox potential determines pro-inflammatory IL-1beta levels. PLoS One 4:e5017. doi:10.1371/journal.pone.0005017

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Janeway CA Jr (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54(Pt 1):1–13

    Article  CAS  PubMed  Google Scholar 

  68. Jourdan T, Godlewski G, Cinar R et al (2013) Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat Med 19:1132–1140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jung CH, Jun CB, Ro SH et al (2009) ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20:1992–2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kaczmarek A, Vandenabeele P, Krysko DV (2013) Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38:209–223

    Article  CAS  PubMed  Google Scholar 

  71. Kaiser WJ, Upton JW, Long AB et al (2011) RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471:368–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kambas K, Mitroulis I, Apostolidou E et al (2012) Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis. PLoS One 7:e45427. doi:10.1371/journal.pone.0045427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kamo N, Ke B, Ghaffari AA et al (2013) ASC/caspase-1/IL-1beta signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia/reperfusion injury. Hepatology 58:351–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kang R, Chen R, Zhang Q et al (2014) HMGB1 in health and disease. Mol Aspects Med 40:1–116

    Article  CAS  PubMed  Google Scholar 

  75. Kang R, Lotze MT, Zeh HJ et al (2014) Cell death and DAMPs in acute pancreatitis. Mol Med 20:466–477

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Kang R, Tang D (2012) PKR-dependent inflammatory signals. Sci Signal 5:pe47. doi:10.1126/scisignal.2003511

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kang R, Zeh HJ, Lotze MT et al (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18:571–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kang R, Zhang Q, Zeh HJ 3rd et al (2013) HMGB1 in cancer: good, bad, or both? Clin Cancer Res 19:4046–4057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kazama H, Ricci JE, Herndon JM et al (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29:21–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Konno H, Konno K, Barber GN (2013) Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 155:688–698

    Article  CAS  PubMed  Google Scholar 

  82. Kono H, Rock KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8:279–289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kovalenko A, Kim JC, Kang TB et al (2009) Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. J Exp Med 206:2161–2177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72

    Article  CAS  PubMed  Google Scholar 

  85. Kroemer G, Galluzzi L, Vandenabeele P et al (2009) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16:3–11

    Article  CAS  PubMed  Google Scholar 

  86. Kroemer G, Levine B (2008) Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 9:1004–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40:280–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Krysko DV, Garg AD, Kaczmarek A et al (2012) Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 12:860–875

    Article  CAS  PubMed  Google Scholar 

  89. Lau A, Wang S, Jiang J et al (2013) RIPK3-mediated necroptosis promotes donor kidney inflammatory injury and reduces allograft survival. Am J Transplant 13:2805–2818

    Article  CAS  PubMed  Google Scholar 

  90. Leblanc PM, Doggett TA, Choi J et al (2014) An immunogenic peptide in the a-box of HMGB1 reverses apoptosis-induced tolerance through RAGE. J Biol Chem 289:7777–7786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lee J, Kim HR, Quinley C et al (2012) Autophagy suppresses interleukin-1beta (IL-1beta) signaling by activation of p62 degradation via lysosomal and proteasomal pathways. J Biol Chem 287:4033–4040

    Article  CAS  PubMed  Google Scholar 

  92. Leemans JC, Cassel SL, Sutterwala FS (2011) Sensing damage by the NLRP3 inflammasome. Immunol Rev 243:152–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Levine B (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120:159–162

    CAS  PubMed  Google Scholar 

  94. Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469:323–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Li J, McQuade T, Siemer AB et al (2012) The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150:339–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99

    Article  CAS  PubMed  Google Scholar 

  97. Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370:455–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Liu G, Wang J, Park YJ et al (2008) High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine. J Immunol 181:4240–4246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Liu L, Yang M, Kang R et al (2014) HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochem Biophys Res Commun 450:851–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Liu X, Kim CN, Yang J et al (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157

    Article  CAS  PubMed  Google Scholar 

  101. Liu Y, Levine B (2014) Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ 22:367–376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Liu Y, Shoji-Kawata S, Sumpter RM Jr et al (2013) Autosis is a Na+, K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci U S A 110:20364–20371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lu B, Nakamura T, Inouye K et al (2012) Novel role of PKR in inflammasome activation and HMGB1 release. Nature 488:670–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Maiuri MC, Zalckvar E, Kimchi A et al (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752

    Article  CAS  PubMed  Google Scholar 

  105. Martinez J, Almendinger J, Oberst A et al (2011) Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. Proc Natl Acad Sci U S A 108:17396–17401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265

    Article  CAS  PubMed  Google Scholar 

  107. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045

    Article  CAS  PubMed  Google Scholar 

  108. McPhee CK, Logan MA, Freeman MR et al (2010) Activation of autophagy during cell death requires the engulfment receptor Draper. Nature 465:1093–1096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454:428–435

    Article  CAS  PubMed  Google Scholar 

  110. Mehlen P, Bredesen DE (2011) Dependence receptors: from basic research to drug development. Sci Signal 4:mr2. doi:10.1126/scisignal.2001521

    Article  PubMed  Google Scholar 

  111. Metzler KD, Goosmann C, Lubojemska A et al (2014) A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep 8:883–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Mitroulis I, Kambas K, Chrysanthopoulou A et al (2011) Neutrophil extracellular trap formation is associated with IL-1beta and autophagy-related signaling in gout. PLoS One 6:e29318. doi:10.1371/journal.pone.0029318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132

    Article  CAS  PubMed  Google Scholar 

  114. Munz C (2009) Enhancing immunity through autophagy. Annu Rev Immunol 27:423–449

    Article  CAS  PubMed  Google Scholar 

  115. Murphy JM, Czabotar PE, Hildebrand JM et al (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39:443–453

    Article  CAS  PubMed  Google Scholar 

  116. Murrow L, Debnath J (2013) Autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease. Annu Rev Pathol 8:105–137

    Article  CAS  PubMed  Google Scholar 

  117. Nakahira K, Haspel JA, Rathinam VA et al (2010) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12:222–230

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Newton K, Dugger DL, Wickliffe KE et al (2014) Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 343:1357–1360

    Article  CAS  PubMed  Google Scholar 

  119. Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61

    Article  CAS  PubMed  Google Scholar 

  120. Oka T, Hikoso S, Yamaguchi O et al (2012) Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485:251–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Park MA, Curiel DT, Koumenis C et al (2008) PERK-dependent regulation of HSP70 expression and the regulation of autophagy. Autophagy 4:364–367

    Article  CAS  PubMed  Google Scholar 

  122. Paul S, Kashyap AK, Jia W et al (2012) Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-kappaB. Immunity 36:947–958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Qu X, Zou Z, Sun Q et al (2007) Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128:931–946

    Article  CAS  PubMed  Google Scholar 

  124. Rathinam VA, Vanaja SK, Fitzgerald KA (2012) Regulation of inflammasome signaling. Nat Immunol 13:333–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Ravichandran KS (2010) Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 207:1807–1817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ravichandran KS (2011) Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 35:445–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Remijsen Q, Kuijpers TW, Wirawan E et al (2011) Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ 18:581–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Rickard JA, O’Donnell JA, Evans JM et al (2014) RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157:1175–1188

    Article  CAS  PubMed  Google Scholar 

  129. Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5:897–907

    Article  CAS  PubMed  Google Scholar 

  130. Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Ryan GB, Majno G (1977) Acute inflammation. A review. Am J Pathol 86:183–276

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Saitoh T, Fujita N, Hayashi T et al (2009) Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A 106:20842–20846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Saitoh T, Fujita N, Jang MH et al (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456:264–268

    Article  CAS  PubMed  Google Scholar 

  134. Saitoh T, Satoh T, Yamamoto N et al (2011) Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity 34:352–363

    Article  CAS  PubMed  Google Scholar 

  135. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195

    Article  CAS  PubMed  Google Scholar 

  136. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  CAS  PubMed  Google Scholar 

  137. Schweichel JU, Merker HJ (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7:253–266

    Article  CAS  PubMed  Google Scholar 

  138. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Seong SY, Matzinger P (2004) Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol 4:469–478

    Article  CAS  PubMed  Google Scholar 

  140. Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197

    Article  CAS  PubMed  Google Scholar 

  141. Shimada K, Crother TR, Karlin J et al (2012) Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36:401–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Spisek R, Charalambous A, Mazumder A et al (2007) Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. Blood 109:4839–4845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Steinberg BE, Grinstein S (2007) Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Sci STKE 2007:pe11

    Article  PubMed  Google Scholar 

  144. Sun L, Wang H, Wang Z et al (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148:213–227

    Article  CAS  PubMed  Google Scholar 

  145. Susin SA, Lorenzo HK, Zamzami N et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446

    Article  CAS  PubMed  Google Scholar 

  146. Tabas I, Glass CK (2013) Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 339:166–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    Article  CAS  PubMed  Google Scholar 

  148. Takahashi N, Vereecke L, Bertrand MJ et al (2014) RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513:95–99

    Article  CAS  PubMed  Google Scholar 

  149. Tang D, Billiar TR, Lotze MT (2012) A Janus tale of two active high mobility group box 1 (HMGB1) redox states. Mol Med 18:1360–1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Tang D, Kang R, Cheh CW et al (2010) HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 29:5299–5310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Tang D, Kang R, Coyne CB et al (2012) PAMPs and DAMPs: signal 0 s that spur autophagy and immunity. Immunol Rev 249:158–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Tang D, Kang R, Livesey KM et al (2010) Endogenous HMGB1 regulates autophagy. J Cell Biol 190:881–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Tang D, Kang R, Livesey KM et al (2011) High-mobility group box 1 is essential for mitochondrial quality control. Cell Metab 13:701–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Tang D, Kang R, Zeh HJ 3rd et al (2010) High-mobility group box 1 and cancer. Biochim Biophys Acta 1799:131–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Tang D, Kang R, Zeh HJ et al (2011) High-mobility group box 1, oxidative stress, and disease. Antioxid Redox Signal 14:1315–1335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Tang D, Lotze MT (2012) Tumor immunity times out: TIM-3 and HMGB1. Nat Immunol 13:808–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Teplova I, Lozy F, Price S et al (2013) ATG proteins mediate efferocytosis and suppress inflammation in mammary involution. Autophagy 9:459–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Thorburn J, Horita H, Redzic J et al (2009) Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death Differ 16:175–183

    Article  CAS  PubMed  Google Scholar 

  159. Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747

    Article  CAS  PubMed  Google Scholar 

  160. Tsung A, Sahai R, Tanaka H et al (2005) The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med 201:1135–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Urbonaviciute V, Furnrohr BG, Weber C et al (2007) Factors masking HMGB1 in human serum and plasma. J Leukoc Biol 81:67–74

    Article  CAS  PubMed  Google Scholar 

  162. van den Brink MR, Burakoff SJ (2002) Cytolytic pathways in haematopoietic stem-cell transplantation. Nat Rev Immunol 2:273–281

    Article  PubMed  CAS  Google Scholar 

  163. van Loo G, van Gurp M, Depuydt B et al (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 9:20–26

    Article  PubMed  Google Scholar 

  164. Vandanmagsar B, Youm YH, Ravussin A et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Vanden Berghe T, Linkermann A, Jouan-Lanhouet S et al (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15:135–147

    Article  CAS  PubMed  Google Scholar 

  166. Vandenabeele P, Galluzzi L, Vanden Berghe T et al (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714

    Article  CAS  PubMed  Google Scholar 

  167. Venereau E, Casalgrandi M, Schiraldi M et al (2012) Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med 209:1519–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Vernon PJ, Tang D (2013) Eat-me: autophagy, phagocytosis, and reactive oxygen species signaling. Antioxid Redox Signal 18:677–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Wang C, Youle RJ (2009) The role of mitochondria in apoptosis*. Annu Rev Genet 43:95–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Wang H, Bloom O, Zhang M et al (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251

    Article  CAS  PubMed  Google Scholar 

  171. Wang Y, Martins I, Ma Y et al (2013) Autophagy-dependent ATP release from dying cells via lysosomal exocytosis. Autophagy 9:1624–1625

    Article  CAS  PubMed  Google Scholar 

  172. Welz PS, Wullaert A, Vlantis K et al (2011) FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477:330–334

    Article  CAS  PubMed  Google Scholar 

  173. Wen H, Ting JP, O’Neill LA (2012) A role for the NLRP3 inflammasome in metabolic diseases – did Warburg miss inflammation? Nat Immunol 13:352–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Xu J, Zhang X, Monestier M et al (2011) Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 187:2626–2631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Xu J, Zhang X, Pelayo R et al (2009) Extracellular histones are major mediators of death in sepsis. Nat Med 15:1318–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12:814–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22:124–131

    Article  CAS  PubMed  Google Scholar 

  178. Yipp BG, Petri B, Salina D et al (2012) Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 18:1386–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12:9–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59

    Article  CAS  PubMed  Google Scholar 

  181. Zaki MH, Lamkanfi M, Kanneganti TD (2011) The Nlrp3 inflammasome: contributions to intestinal homeostasis. Trends Immunol 32:171–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Zhang Q, Kang R, Zeh HJ 3rd et al (2013) DAMPs and autophagy: cellular adaptation to injury and unscheduled cell death. Autophagy 9:451–458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Zhang Q, Raoof M, Chen Y et al (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Zhang Y, Li W, Zhu S et al (2012) Tanshinone IIA sodium sulfonate facilitates endocytic HMGB1 uptake. Biochem Pharmacol 84:1492–1500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Zhou R, Yazdi AS, Menu P et al (2010) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225

    Article  PubMed  CAS  Google Scholar 

  186. Zhou W, Yuan J (2014) Necroptosis in health and diseases. Semin Cell Dev Biol 35C:14–23

    Article  CAS  Google Scholar 

  187. Zitvogel L, Kepp O, Kroemer G (2010) Decoding cell death signals in inflammation and immunity. Cell 140:798–804

    Article  CAS  PubMed  Google Scholar 

  188. Zong WX, Thompson CB (2006) Necrotic death as a cell fate. Genes Dev 20:1–15

    Article  CAS  PubMed  Google Scholar 

  189. Zou J, Kawai T, Tsuchida T et al (2013) Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis. Immunity 38:717–728

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We apologize to the researchers who were not referenced due to space limitations. We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by the National Institutes of Health (NIH) (R01CA160417 to D.T.) and the American Association for Cancer Research (AACR) (13-20-25-TANG to D.T.).

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  1. Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Rui Kang & Daolin Tang

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  1. Centre de Recherche des Cordeliers, UMRS 1138 – Team 11,, Paris, France

    Maria Chiara Maiuri

  2. Multi Medica Fondazione Onlus, Milan, Italy

    Daniela De Stefano

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Kang, R., Tang, D. (2016). What Is the Pathobiology of Inflammation to Cell Death? Apoptosis, Necrosis, Necroptosis, Autophagic Cell Death, Pyroptosis, and NETosis. In: Maiuri, M., De Stefano, D. (eds) Autophagy Networks in Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-30079-5_5

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