| First Author | de Vasconcelos NM | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 4 | Pages | 107959 |
| PubMed ID | 32726624 | Mgi Jnum | J:323547 |
| Mgi Id | MGI:6715841 | Doi | 10.1016/j.celrep.2020.107959 |
| Citation | de Vasconcelos NM, et al. (2020) An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages. Cell Rep 32(4):107959 |
| abstractText | Pyroptosis has emerged as a key mechanism by which inflammasomes promote host defense against microbial pathogens and sterile inflammation. Gasdermin D (GSDMD)-mediated cell lysis is a hallmark of pyroptosis, but our understanding of cell death signaling during pyroptosis is fragmented. Here, we show that independently of GSDMD-mediated plasma membrane permeabilization, inflammasome receptors engage caspase-1 and caspase-8, both of which redundantly promote activation of apoptotic executioner caspase-3 and caspase-7 in pyroptotic macrophages. Impaired GSDMD pore formation downstream of caspase-1 and caspase-8 activation suffices to unmask the apoptotic phenotype of pyroptotic macrophages. Combined inactivation of initiator caspase-1 and caspase-8, or executioner caspase-3 and caspase-7, is required to abolish inflammasome-induced DEVDase activity during pyroptosis and in apoptotic Gsdmd(-/-) cells. Collectively, these results unveil a robust apoptotic caspase network that is activated in parallel to GSDMD-mediated plasma membrane permeabilization and safeguards cell death induction in pyroptotic macrophages. |
