Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP


ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Russell Vance 

PROVIDER: E-GEOD-16943 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP.

McWhirter Sarah M SM   Barbalat Roman R   Monroe Kathryn M KM   Fontana Mary F MF   Hyodo Mamoru M   Joncker Nathalie T NT   Ishii Ken J KJ   Akira Shizuo S   Colonna Marco M   Chen Zhijian J ZJ   Fitzgerald Katherine A KA   Hayakawa Yoshihiro Y   Vance Russell E RE  

The Journal of experimental medicine 20090803 9


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 eukaryo  ...[more]

Similar Datasets

2009-07-22 | GSE16943 | GEO
2015-02-13 | E-GEOD-65905 | biostudies-arrayexpress
2023-12-12 | MTBLS7053 | MetaboLights
2015-02-13 | GSE65905 | GEO
2017-11-01 | E-MTAB-5328 | biostudies-arrayexpress
2013-12-31 | E-GEOD-26968 | biostudies-arrayexpress
2013-10-09 | GSE37973 | GEO
| PRJNA726970 | ENA
2013-12-31 | GSE26968 | GEO
2017-06-01 | E-MTAB-5410 | biostudies-arrayexpress