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. Author manuscript; available in PMC: 2016 Jun 15.
Published in final edited form as: Cell Rep. 2016 Jun 2;15(11):2449–2461. doi: 10.1016/j.celrep.2016.05.032

FIGURE 7. Regulation of survival and necroptosis in macrophages.

FIGURE 7

During an infection, the determination of TNF-induced necroptosis is subject to cross-regulation by other receptor pathways. I: TLR4 activates CASPASE-8 through a TRIF-dependent manner to proteolyze and remove CYLD. CYLD is essential for TNF-induced necroptosis, and so its removal prevents macrophages from undergoing necroptosis that can be induced by the TNF produced during bacterial infection. II: Inhibition of CASPASE-8 stabilizes CYLD and this results in necroptosis mediated by auto-produced TNF signaling via CYLD. Type I IFN plays a licensing role because it is required for the induction of TNFR2, MLKL and other uncharacterized molecules that are essential for TNF-mediated necroptosis.