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From the same journal

From the same journal

Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion

Research output: Contribution to journalArticlepeer-review


  • Kaiwen W Chen
  • Kate E Lawlor
  • Jessica B von Pein
  • Dave Boucher
  • Motti Gerlic
  • Ben A Croker
  • Jelena S Bezbradica
  • James E Vince
  • Kate Schroder


Publication details

JournalJournal of Immunology
DateAccepted/In press - 19 Mar 2018
DateE-pub ahead of print - 15 May 2018
DatePublished (current) - 15 May 2018
Issue number10
Number of pages6
Pages (from-to)3341-3346
Early online date15/05/18
Original languageEnglish


The mammalian inhibitor of apoptosis proteins (IAPs) are key regulators of cell death and inflammation. A major function of IAPs is to block the formation of a cell death-inducing complex, termed the ripoptosome, which can trigger caspase-8-dependent apoptosis or caspase-independent necroptosis. Recent studies report that upon TLR4 or TNF receptor 1 (TNFR1) signaling in macrophages, the ripoptosome can also induce NLRP3 inflammasome formation and IL-1β maturation. Whether neutrophils have the capacity to assemble a ripoptosome to induce cell death and inflammasome activation during TLR4 and TNFR1 signaling is unclear. In this study, we demonstrate that murine neutrophils can signal via TNFR1-driven ripoptosome assembly to induce both cell death and IL-1β maturation. However, unlike macrophages, neutrophils suppress TLR4-dependent cell death and NLRP3 inflammasome activation during IAP inhibition via deficiencies in the CD14/TRIF arm of TLR4 signaling.

Bibliographical note

Copyright © 2018 by The American Association of Immunologists, Inc.

    Research areas

  • Animals, Apoptosis/drug effects, Caspases/metabolism, Cell Death/drug effects, Inflammasomes/metabolism, Inflammation/metabolism, Inhibitor of Apoptosis Proteins/metabolism, Interleukin-1beta/metabolism, Lipopolysaccharides/pharmacology, Macrophages/drug effects, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Necrosis/metabolism, Neutrophils/drug effects, Receptors, Tumor Necrosis Factor, Type I/metabolism, Signal Transduction/physiology, Toll-Like Receptor 4/metabolism, Tumor Necrosis Factors/metabolism

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