Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals

Bezbradica, Jelena S., Coll, Rebecca C. and Schroder, Kate (2016) Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. Cellular and Molecular Immunology, 1-9. doi:doi:10.1038/cmi.2016.11


Author Bezbradica, Jelena S.
Coll, Rebecca C.
Schroder, Kate
Title Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals
Journal name Cellular and Molecular Immunology   Check publisher's open access policy
ISSN 1672-7681
2042-0226
Publication date 2016-03-21
Sub-type Article (original research)
DOI doi:10.1038/cmi.2016.11
Open Access Status DOI
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Abstract Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.
Keyword Inflammasome
NLRP3
Sterile inflammation
TNF
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Advance online publication 21 March 2016

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 01 Apr 2016, 15:57:07 EST by Dr Kate Schroder on behalf of School of Chemistry & Molecular Biosciences