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

Chen KW., Lawlor KE., von Pein JB., Boucher D., Gerlic M., Croker BA., Bezbradica JS., Vince JE., Schroder K.

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.

DOI

10.4049/jimmunol.1701620

Type

Journal article

Journal

J immunol

Publication Date

15/05/2018

Volume

200

Pages

3341 - 3346

Keywords

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

Permalink Original publication