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 language | English (US) |
|---|---|
| Pages (from-to) | 2019-2026 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 192 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2014 |
| Externally published | Yes |
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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 journal › Review article
}
TY - JOUR
T1 - True grit
T2 - Programmed necrosis in antiviral host defense, inflammation, and immunogenicity
AU - Mocarski, Edward S.
AU - Kaiser, William
AU - Livingston-Rosanoff, Devon
AU - Upton, Jason W.
AU - Daley-Bauer, Lisa P.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84896541259&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1302426
DO - 10.4049/jimmunol.1302426
M3 - Review article
C2 - 24563506
AN - SCOPUS:84896541259
VL - 192
SP - 2019
EP - 2026
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -