Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 publication

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