NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE184678 Query DataSets for GSE184678
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
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.
 
Overall design We sequenced 2 types of mouse knockout models and 1 wild-type, each with 3 replicates
 
Contributor(s) Webb A, Amer AO, Eltobgy M
Citation(s) 35588457
Submission date Sep 23, 2021
Last update date Feb 16, 2023
Contact name Amy Hite
Organization name The Ohio State University
Department Biomedical Informatics
Street address 1800 Cannon Drive 250 Lincoln Tower
City Columbus
State/province OH - Ohio
ZIP/Postal code 43210
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (9)
GSM5595286 CSP11.1
GSM5595287 CSP11.2
GSM5595288 CSP11.3
Relations
BioProject PRJNA765615
SRA SRP338428

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE184678_mRNA_voom_Expr.txt.gz 1.0 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.