IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection.
J Immunol
; 200(4): 1489-1495, 2018 02 15.
Article
en En
| MEDLINE
| ID: mdl-29321274
ABSTRACT
Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms, including the nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin domain containing 3 (NLRP3) inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection. Both inflammasome-dependent responses and induction of apoptosis and necroptosis are reduced in cells lacking IRF1 infected with IAV. The observed reduction in inflammasome activation and cell death in IRF1-deficient cells during IAV infection correlates with reduced levels of Z-DNA binding protein 1 (ZBP1), a key molecule mediating IAV-induced inflammatory and cell death responses. We further demonstrate IRF1 as a transcriptional regulator of ZBP1. Overall, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteínas
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Regulación de la Expresión Génica
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Infecciones por Orthomyxoviridae
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Factor 1 Regulador del Interferón
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Inflamasomas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2018
Tipo del documento:
Article