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

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

doi:10.4049/jimmunol.1701620

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

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

Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	3341-3346
Number of pages	6
Journal	Journal of Immunology
Volume	200
Issue number	10
Early online date	15 May 2018
DOIs	https://doi.org/10.4049/jimmunol.1701620
Publication status	Published - 15 May 2018

Bibliographical note

Keywords

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

Access to Document

10.4049/jimmunol.1701620

https://espace.library.uq.edu.au/view/UQ:728340

Cite this

Chen, K. W., Lawlor, K. E., von Pein, J. B., Boucher, D., Gerlic, M., Croker, B. A., Bezbradica, J. S., Vince, J. E., & Schroder, K. (2018). Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion. Journal of Immunology, 200(10), 3341-3346. https://doi.org/10.4049/jimmunol.1701620

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

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.",

keywords = "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",

author = "Chen, {Kaiwen W} and Lawlor, {Kate E} and {von Pein}, {Jessica B} and Dave Boucher and Motti Gerlic and Croker, {Ben A} and Bezbradica, {Jelena S} and Vince, {James E} and Kate Schroder",

note = "Copyright {\textcopyright} 2018 by The American Association of Immunologists, Inc.",

year = "2018",

month = may,

day = "15",

doi = "10.4049/jimmunol.1701620",

language = "English",

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Chen, KW, Lawlor, KE, von Pein, JB, Boucher, D, Gerlic, M, Croker, BA, Bezbradica, JS, Vince, JE & Schroder, K 2018, 'Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion', Journal of Immunology, vol. 200, no. 10, pp. 3341-3346. https://doi.org/10.4049/jimmunol.1701620

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T1 - Cutting Edge

T2 - Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion

AU - Chen, Kaiwen W

AU - Lawlor, Kate E

AU - von Pein, Jessica B

AU - Boucher, Dave

AU - Gerlic, Motti

AU - Croker, Ben A

AU - Bezbradica, Jelena S

AU - Vince, James E

AU - Schroder, Kate

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis/drug effects

KW - Caspases/metabolism

KW - Cell Death/drug effects

KW - Inflammasomes/metabolism

KW - Inflammation/metabolism

KW - Inhibitor of Apoptosis Proteins/metabolism

KW - Interleukin-1beta/metabolism

KW - Lipopolysaccharides/pharmacology

KW - Macrophages/drug effects

KW - Mice

KW - Mice, Inbred C57BL

KW - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism

KW - Necrosis/metabolism

KW - Neutrophils/drug effects

KW - Receptors, Tumor Necrosis Factor, Type I/metabolism

KW - Signal Transduction/physiology

KW - Toll-Like Receptor 4/metabolism

KW - Tumor Necrosis Factors/metabolism

U2 - 10.4049/jimmunol.1701620

DO - 10.4049/jimmunol.1701620

M3 - Article

C2 - 29661823

SN - 0022-1767

VL - 200

SP - 3341

EP - 3346

JO - Journal of Immunology

JF - Journal of Immunology

IS - 10

ER -