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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 11, 2016 |
| Title |
ZBP1 is a cytosolic RNA virus sensor driving activation of the NLRP3 inflammasome, pyroptosis, necroptosis and apoptosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation.
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| Overall design |
We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
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| Contributor(s) |
Kuriakose T, Man SM, Neale G, Kanneganti T |
| Citation(s) |
27917412 |
| Submission date |
Feb 05, 2016 |
| Last update date |
Mar 14, 2019 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
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| Organization name |
St Jude Childrens Research Hospital
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| Department |
Hartwell Center
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (4)
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| GSM2055168 |
Wild-type BMDM infected with influenza A virus PR8, rep 1 |
| GSM2055169 |
Wild-type BMDM infected with influenza A virus PR8, rep 2 |
| GSM2055170 |
Ifnar1-/- BMDM infected with influenza A virus PR8, rep 1 |
| GSM2055171 |
Ifnar1-/- BMDM infected with influenza A virus PR8, rep 2 |
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| Relations |
| BioProject |
PRJNA311029 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77611_RAW.tar |
35.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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