The murine neutrophil NLRP3 inflammasome is activated by soluble but not particulate or crystalline agonists.

Details

Serval ID
serval:BIB_2DEEE048558E
Type
Article: article from journal or magazin.
Collection
Publications
Title
The murine neutrophil NLRP3 inflammasome is activated by soluble but not particulate or crystalline agonists.
Journal
European journal of immunology
Author(s)
Chen K.W., Bezbradica J.S., Groß C.J., Wall A.A., Sweet M.J., Stow J.L., Schroder K.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
04/2016
Peer-reviewed
Oui
Volume
46
Number
4
Pages
1004-1010
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Neutrophils express pattern recognition receptors (PRRs) and regulate immune responses via PRR-dependent cytokine production. An emerging theme is that neutrophil PRRs often exhibit cell type-specific adaptations in their signalling pathways. This prompted us to examine inflammasome signalling by the PRR NLRP3 in murine neutrophils, in comparison to well-established NLRP3 signalling pathways in macrophages. Here, we demonstrate that while murine neutrophils can indeed signal via the NLRP3 inflammasome, neutrophil NLRP3 selectively responds to soluble agonists but not to the particulate/crystalline agonists that trigger NLRP3 activation in macrophages via phagolysosomal rupture. In keeping with this, alum did not trigger IL-1β production from human PMN, and the lysosomotropic peptide Leu-Leu-OMe stimulated only weak NLRP3-dependent IL-1β production from murine neutrophils, suggesting that lysosomal rupture is not a strong stimulus for NLRP3 activation in neutrophils. We validated our in vitro findings for poor neutrophil NLRP3 responses to particles in vivo, where we demonstrated that neutrophils do not significantly contribute to alum-induced IL-1β production in mice. In all, our studies highlight that myeloid cell identity and the nature of the danger signal can strongly influence signalling by a single PRR, thus shaping the nature of the resultant immune response.
Keywords
Alum Compounds/pharmacology, Animals, Carrier Proteins/genetics, Carrier Proteins/immunology, Cells, Cultured, Dipeptides/pharmacology, Humans, Interleukin-1beta/biosynthesis, Lipopolysaccharides/pharmacology, Macrophage Activation/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein, Neutrophil Activation/immunology, Neutrophils/immunology, Peritonitis/chemically induced, Peritonitis/immunology, Receptors, Pattern Recognition/immunology, Signal Transduction/immunology, IL-1β · Inflammasomes · Lysosomal rupture · Neutrophils · NLRP3
Pubmed
Web of science
Open Access
Yes
Create date
22/09/2018 20:04
Last modification date
21/08/2019 5:35
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