ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways

The interferon-inducible protein Z-DNA binding protein 1 (ZBP1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) was identified as a dsDNA sensor, which instigates innate immune responses. However, this classification has been disputed and whether ZBP1 functions as a...

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Published inScience immunology Vol. 1; no. 2
Main Authors Kuriakose, Teneema, Man, Si Ming, Malireddi, R K Subbarao, Karki, Rajendra, Kesavardhana, Sannula, Place, David E, Neale, Geoffrey, Vogel, Peter, Kanneganti, Thirumala-Devi
Format Journal Article
LanguageEnglish
Published United States 05.08.2016
Subjects
IFNs
ZBP1
pyroptosis
caspase-8
RIPK3
inflammasome
influenza virus
NLRP3
apoptosis
DAI
caspase-1
necroptosis
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Summary:The interferon-inducible protein Z-DNA binding protein 1 (ZBP1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) was identified as a dsDNA sensor, which instigates innate immune responses. However, this classification has been disputed and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. Herein, we demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the RIPK1-RIPK3-Caspase-8 axis. ZBP1 regulates NLRP3 inflammasome activation as well as induction of apoptosis, necroptosis and pyroptosis in IAV-infected cells. Importantly, ZBP1 deficiency protected mice from mortality during IAV infection owing to reduced inflammatory responses and epithelial damage. Overall, these findings indicate that ZBP1 is an innate immune sensor of IAV and highlight its importance in the pathogenesis of IAV infection.
ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.aag2045