TY - JOUR
T1 - ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways
AU - Kuriakose, Teneema
AU - Man, Si Ming
AU - Subbarao Malireddi, R. K.
AU - Karki, Rajendra
AU - Kesavardhana, Sannula
AU - Place, David E.
AU - Neale, Geoffrey
AU - Vogel, Peter
AU - Kanneganti, Thirumala Devi
N1 - Publisher Copyright:
2016 © The Authors.
PY - 2016
Y1 - 2016
N2 - The interferon (IFN)–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 double-stranded DNA 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. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)–RIPK3–caspase-8 axis. ZBP1 regulates NLRP3 (nucleotide and oligomerization domain, leucine-rich repeat–containing protein family, pyrin domain containing 3) inflammasome activation as well as induction of apoptosis, necroptosis, and pyroptosis in IAV-infected cells. 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.
AB - The interferon (IFN)–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 double-stranded DNA 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. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)–RIPK3–caspase-8 axis. ZBP1 regulates NLRP3 (nucleotide and oligomerization domain, leucine-rich repeat–containing protein family, pyrin domain containing 3) inflammasome activation as well as induction of apoptosis, necroptosis, and pyroptosis in IAV-infected cells. 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.
UR - http://www.scopus.com/inward/record.url?scp=85022040336&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.aag2045
DO - 10.1126/sciimmunol.aag2045
M3 - Article
SN - 2470-9468
VL - 1
JO - Science immunology
JF - Science immunology
IS - 2
M1 - aag2045
ER -