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J Immunol. 2018 May 15;200(10):3341-3346. doi: 10.4049/jimmunol.1701620. Epub 2018 Apr 16.

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

Author information

1
Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia.
2
Division of Inflammation, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
3
Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
4
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; and.
5
Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115.
6
Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia; K.Schroder@imb.uq.edu.au.

Abstract

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.

PMID:
29661823
DOI:
10.4049/jimmunol.1701620
[Indexed for MEDLINE]
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