Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition

Tate, Michelle D., Ong, James D. H., Dowling, Jennifer K., McAuley, Julie L., Robertson, Avril B., Latz, Eicke, Drummond, Grant R., Cooper, Matthew A., Hertzog, Paul J. and Mansell, Ashley (2016) Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Scientific Reports, 6 . doi:10.1038/srep27912


Author Tate, Michelle D.
Ong, James D. H.
Dowling, Jennifer K.
McAuley, Julie L.
Robertson, Avril B.
Latz, Eicke
Drummond, Grant R.
Cooper, Matthew A.
Hertzog, Paul J.
Mansell, Ashley
Title Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-06-10
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep27912
Open Access Status DOI
Volume 6
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Abstract The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity.
Keyword Inflammasome NLRP3
Pathogen associated molecular patterns (PAMPs)
Danger associated molecular patterns (DAMPs)
Influenza A virus (IAV)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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