A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP
Authors
McWhirter, Sarah M.Barbalat, Roman
Monroe, Kathryn M.
Fontana, Mary F.
Hyodo, Mamoru
Joncker, Nathalie T.
Ishii, Ken J.
Akira, Shizuo
Colonna, Marco
Cheng, Zhiliang
Fitzgerald, Katherine A.
Hayakawa, Yoshihiro
Vance, Russell E.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDepartment of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2009-08-05Keywords
AnimalsCell Line, Tumor
Cyclic GMP
Cytosol
DNA Primers
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
Immunity, Innate
Immunoblotting
Interferon Type I
Mice
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Second Messenger Systems
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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. 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 c-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, nuclear factor kappaB, 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.Source
J Exp Med. 2009 Aug 31;206(9):1899-911. Epub 2009 Aug 3. Link to article on publisher's siteDOI
10.1084/jem.20082874Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35228PubMed ID
19652017Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1084/jem.20082874