Gene expression profiles in TICAM1 knockout and wild-type MEFs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE78205 | GEO | 2016/07/29
SECONDARY ACCESSION(S): PRJNA312923
REPOSITORIES: GEO
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Project description:TICAM1 knockout and wild-type (TICAM1 knockout MEFs with restored TICAM1 expression) MEFs were treated by c-di-GMP or DMSO for 4 hours. Total RNA was analyzed via Illumina Mouse Ref-8 V2. Changes in gene induction, especially of interferon-stimulated genes, between c-di-GMP and DMSO treated cells were examined. Total RNA from c-di-GMP or DMSO treated wild-type MEFs, c-di-GMP or DMSO treated TICAM1 knockout MEFs were analyzed. Gene expression was compared between c-di-GMP treated and DMSO treated samples.
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Project description:The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. Here we provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by cyclic-di- GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, NF-!B and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways.Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. Three-condition experiment: macrophages transfected with mono-GMP (negative control), double-stranded DNA (positive control), or cyclic-di-GMP (experimental condition). Biological replicates: two, independently treated, harvested, and hybridized to arrays. One replicate per array, except two technical replicates were performed for one of the positive control samples.
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