title: An evolutionary perspective on the necroptotic pathway.
abstract: Throughout the animal kingdom, innate immune receptors protect the organism from microbial intruders by activating pathways that mediate inflammation and pathogen clearance. Necroptosis contributes to the innate immune response by killing pathogen-infected cells and by alerting the immune system through the release of danger signals. Components of the necroptotic signaling axis - TIR-domain-containing adapter-inducing interferon-β (TRIF), Z-DNA sensor DAI, receptor-interacting kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL) - are therefore expected to be found in all animals. However, a phylogenetic analysis reveals that the necroptotic axis, except for RIPK1, is poorly conserved in the animal kingdom, suggesting that alternative mechanisms regulate necroptosis in these species or that necroptosis would apparently be absent. These findings question the universal role of necroptosis during innate immunity in the animal kingdom.
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dondelinger
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium.
authors.forename: Paco
authors.initials: P
authors.lastname: Hulpiau
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Saeys
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium.
authors.forename: Mathieu J M
authors.initials: MJM
authors.lastname: Bertrand
authors.affiliation: VIB Inflammation Research Center, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde-Ghent, 9052, Belgium. Electronic address: Peter.Vandenabeele@irc.vib-ugent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
mesh_terms: D000818:Animals; D017209:Apoptosis; D005075:Biological Evolution; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009336:Necrosis; D010802:Phylogeny
keywords: DAI; MLKL; RHIM; RIPK1; RIPK3; TRIF