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Series GSE86922 Query DataSets for GSE86922
Status Public on Sep 15, 2016
Title Activity of uncleaved caspase-8 controls anti-bacterial immune defense and TLR-induced cytokine production independent of cell death
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Caspases regulate cell death programs in response to environmental stresses, including infection and inflammation, and are therefore critical for the proper operation of the mammalian immune system.  Caspase-8 is necessary for optimal production of inflammatory cytokines and host defense against infection by multiple pathogens including Yersinia, but whether this is due to death of infected cells or an intrinsic role of caspase-8 in TLR-induced gene expression is unknown. Caspase-8 activation at death signaling complexes results in its autoprocessing and subsequent cleavage and activation of its downstream apoptotic targets. Whether caspase-8 activity is also important for inflammatory gene expression during bacterial infection has not been investigated. Here, we report that caspase-8 plays an essential cell-intrinsic role in innate inflammatory cytokine production in vivo during Yersinia infection. Unexpectedly, we found that caspase-8 enzymatic activity regulates gene expression in response to bacterial infection as well as TLR signaling independently of apoptosis. Using newly-generated mice in which caspase-8 autoprocessing is ablated (Casp8DA/DA), we now demonstrate that caspase-8 enzymatic activity, but not autoprocessing, mediates induction of inflammatory cytokines by bacterial infection and a wide variety of TLR stimuli. Because unprocessed caspase-8 functions in an enzymatic complex with its homolog cFLIP, our findings implicate the caspase-8/cFLIP heterodimer in control of inflammatory cytokines during microbial infection, and provide new insight into regulation of antibacterial immune defense.
 
Overall design Two biological replicates were analyzed for each of 6 conditions (three genotypes; two treatments per genotype)
 
Contributor(s) Beiting D, Philip N, Brodsky I
Citation(s) 27737018
Submission date Sep 14, 2016
Last update date May 15, 2019
Contact name daniel beiting
E-mail beiting@vet.upenn.edu
Organization name University of Pennsylvania
Department Pathobiology
Lab Beiting
Street address 380 S. University Ave
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM2310941 WT_unstim_rep1
GSM2310942 WT_unstim_rep2
GSM2310943 Ripk3_unstim_rep1
Relations
BioProject PRJNA343025
SRA SRP089914

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
GSE86922_Brodsky_GEO_processed.txt.gz 1.7 Mb (ftp)(http) TXT
Raw data are available in SRA
Processed data is available on Series record

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