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Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection

2018; National Academy of Sciences; Volume: 115; Issue: 46 Linguagem: Inglês

10.1073/pnas.1809548115

1091-6490

Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Peng Li, Rachael Nilson, Amy Y. Tang, Anthony Rongvaux, Stephen C. Bunnell, Feng Shao, Douglas R. Green, Alexander Poltorak,

Gout, Hyperuricemia, Uric Acid

Significance Here we demonstrate that Yersinia YopJ-induced murine macrophage death involves caspase-8–induced cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME). The ensuing cell death is rapid, morphologically is similar to pyroptosis, and induces IL-1 release. Recently, both GSDMD and GSDME were reported to be critical effectors of caspase-1/11–driven pyroptosis and caspase-3–dependent secondary necrosis, which prompted the redefinition of pyroptosis as cell death-mediated by gasdermin activation. Our work extends these studies and shows that activation of caspase-8 in the context of TAK1 inhibition results in cleavage of both GSDMD and GSDME, leading to pyroptotic-like cell death. Further study will be needed to determine whether caspase-8 cleaves GSDMD directly or via intermediate substrates.