Distinct sequential death complexes regulate pyroptosis and IL-1β release in response to Yersinia blockade of immune signaling : = Distinct sequential death complexes regulate pyroptosis and IL-1[beta] release in response to Yersinia blockade of immune signaling

Abstract: Pathogen infection of host cells triggers an inflammatory cell death termed pyroptosis via activation of inflammatory caspases. However, blockade of immune signaling kinases by the Yersinia virulence factor YopJ triggers cell death involving both apoptotic caspase-8 and pyroptotic caspase-1. While caspase-1 is normally activated within inflammasomes, Yersinia-induced caspase-1 activation is independent of known inflammasome components. We report that caspase-8 is an essential initiator, while caspase-1 is an essential amplifier of its own activation through two feed-forward loops involving caspase-1 auto-processing and caspase-1–dependent activation of gasdermin D and NLPR3. Notably, while Yersinia-induced caspase-1 activation and cell death are inflammasome-independent, IL-1β release requires NLPR3 inflammasome activation. Mechanistically, caspase-8 is rapidly activated within multiple foci throughout the cell, followed by assembly of a canonical inflammasome speck, indicating that caspase-8 and canonical inflammasome complex assemblies are kinetically and spatially distinct. Our findings reveal that functionally interconnected but distinct death complexes mediate pyroptosis and IL-1β release in response to pathogen blockade of immune signaling

Show object

• Alternative title: Distinct sequential death complexes regulate pyroptosis and IL-1[beta] release in response to Yersinia blockade of immune signaling
• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Science advances. - 10, 30 (2024) , eadl3629, ISSN: 2375-2548

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2024
• Creator: Wertman, Ronit Schwartz ; Yost, Winslow ; Herrmann, Beatrice I. ; Bourne, Christopher M. ; Sorobetea, Daniel ; Go, Christina K. ; Saller, Benedikt S. ; Groß, Olaf ; Scott, Phillip ; Rongvaux, Anthony ; Taabazuing, Cornelius Y. ; Brodsky, Igor E.

Further information

• DOI: 10.1126/sciadv.adl3629
• URN: urn:nbn:de:bsz:25-freidok-2567315
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.