True grit: Programmed necrosis in antiviral host defense, inflammation, and immunogenicity

Edward S. Mocarski, William Kaiser, Devon Livingston-Rosanoff, Jason W. Upton, Lisa P. Daley-Bauer

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

Programmed necrosis mediated by receptor interacting protein kinase (RIP)3 (also called RIPK3) has emerged as an alternate death pathway triggered by TNF family death receptors, pathogen sensors, IFNRs, Ag-specific TCR activation, and genotoxic stress. Necrosis leads to cell leakage and acts as a "trap door," eliminating cells that cannot die by apoptosis because of the elaboration of pathogen-encoded caspase inhibitors. Necrotic signaling requires RIP3 binding to one of three partners-RIP1, DAI, or TRIF-via a common RIP homotypic interaction motif. Once activated, RIP3 kinase targets the pseudokinase mixed lineage kinase domain-like to drive cell lysis. Although necrotic and apoptotic death can enhance T cell cross-priming during infection, mice that lack these extrinsic programmed cell death pathways are able to produce Ag-specific T cells and control viral infection. The entwined relationship of apoptosis and necrosis evolved in response to pathogen-encoded suppressors to support host defense and contribute to inflammation.

Original languageEnglish (US)
Pages (from-to)2019-2026
Number of pages8
JournalJournal of Immunology
Volume192
Issue number5
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

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Receptor-Interacting Protein Serine-Threonine Kinases
Antiviral Agents
Necrosis
Inflammation
Protein Kinases
Phosphotransferases
Cross-Priming
Apoptosis
T-Lymphocytes
Death Domain Receptors
Caspase Inhibitors
Virus Diseases
DNA Damage
Cell Death
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

True grit : Programmed necrosis in antiviral host defense, inflammation, and immunogenicity. / Mocarski, Edward S.; Kaiser, William; Livingston-Rosanoff, Devon; Upton, Jason W.; Daley-Bauer, Lisa P.

In: Journal of Immunology, Vol. 192, No. 5, 01.03.2014, p. 2019-2026.

Research output: Contribution to journalReview article

Mocarski, ES, Kaiser, W, Livingston-Rosanoff, D, Upton, JW & Daley-Bauer, LP 2014, 'True grit: Programmed necrosis in antiviral host defense, inflammation, and immunogenicity', Journal of Immunology, vol. 192, no. 5, pp. 2019-2026. https://doi.org/10.4049/jimmunol.1302426
Mocarski, Edward S. ; Kaiser, William ; Livingston-Rosanoff, Devon ; Upton, Jason W. ; Daley-Bauer, Lisa P. / True grit : Programmed necrosis in antiviral host defense, inflammation, and immunogenicity. In: Journal of Immunology. 2014 ; Vol. 192, No. 5. pp. 2019-2026.
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