title: True grit: programmed necrosis in antiviral host defense, inflammation, and immunogenicity.
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.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
authors.forename: William J
authors.initials: WJ
authors.lastname: Kaiser
authors.forename: Devon
authors.initials: D
authors.lastname: Livingston-Rosanoff
authors.forename: Jason W
authors.initials: JW
authors.lastname: Upton
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Daley-Bauer
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D051379:Mice; D009336:Necrosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D006023:Glycoproteins; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C119724:AGFG1 protein, human; C490620:Ralbp1 protein, mouse; C476286:Ticam1 protein, mouse; C470409:TICAM1 protein, human; C485731:ZBP1 protein, human; C402632:Zbp1 protein, mouse; C119705:RIPK3 protein, human; C485615:Ripk3 protein, mouse