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GEO help: Mouse over screen elements for information. |
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Status |
Public on Feb 16, 2023 |
Title |
Caspase-11 promotes inflammation and thrombosis in SARS-CoV-2 infection |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
SARS-CoV-2 infections are a worldwide health concern, and new treatment strategies are needed for decreasing virus-induced inflammatory tissue damage. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that the innate immunity proteins, human caspase-4 (CASP4), and its mouse homologue, caspase-11 (CASP11), are upregulated in SARS-CoV-2 infections, and that CASP4 expression correlates with severity of SARS-CoV-2 infection in humans. SARS-CoV-2-infected Casp11-/- mice experienced less severe infections in terms of weight loss and lung damage than WT mice. Notably, these phenotypes were not recapitulated in mice lacking the CASP11 downstream effector gasdermin D (Gsdmd-/-), though viral titers were similar in all groups. Global transcriptomics of infected WT and Casp11-/- lungs identified decreased inflammation and neutrophil gene signatures. We confirmed that protein levels of inflammatory mediators IL-1β and CXCL1, and neutrophil infiltration, were decreased in Casp11-/- lungs. Additionally, Casp11-/- lungs expressed less von Willebrand factor, a marker for endothelial dysfunction and more Kruppel-Like Factor 2 (KLF2), a transcription factor with anti-thrombotic functions. Thus, CASP11 is established as an upstream regulator of blood coagulopathy in SARS-CoV-2 infection. Overall, our results demonstrate that CASP11, promotes detrimental SARS-CoV-2-associated inflammation and coagulopathy, identifying CASP11 as a promising drug target for treatment and prevention of tissue damage in COVID-19.
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Overall design |
We sequenced 2 types of mouse knockout models and 1 wild-type, each with 3 replicates
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Contributor(s) |
Webb A, Amer AO, Eltobgy M |
Citation(s) |
35588457 |
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Submission date |
Sep 23, 2021 |
Last update date |
Feb 16, 2023 |
Contact name |
Amy Hite |
Organization name |
The Ohio State University
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Department |
Biomedical Informatics
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Street address |
1800 Cannon Drive 250 Lincoln Tower
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City |
Columbus |
State/province |
OH - Ohio |
ZIP/Postal code |
43210 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (9)
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Relations |
BioProject |
PRJNA765615 |
SRA |
SRP338428 |
Supplementary file |
Size |
Download |
File type/resource |
GSE184678_mRNA_voom_Expr.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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