Innate sensing of bacterial cyclic dinucleotides: More than just STING

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Nature Immunology (Impact Factor: 20). 12/2012; 13(12):1137-9. DOI: 10.1038/ni.2469
Source: PubMed
23 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rapid emergence of multidrug-resistant pathogens, especially Gram-negative bacteria and mycobacteria, represents one of the major medical challenges of the 21st century. The gradual loss of effective classical antibiotics for many bacterial pathogens, combined with an increasing population density and mobility, urgently calls for the development of novel treatments. Here, we discuss the potential of adjuvant immunotherapies to selectively stimulate protective immune responses as a treatment option for bacterial infections. In order to elicit appropriate immune responses and to avoid unwanted inflammatory tissue damage, it is essential to identify ligands and receptor pathways that specifically control protective responses at the site of infection. We summarize existing data and discuss suitable candidate targets for future immunotherapies of infectious diseases.
    No preview · Article · Apr 2013 · Immunotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biofilm development is recognized as a major virulence factor underlying most chronic bacterial infections. When a biofilm community is established, planktonic cells growing in the surroundings of a tissue switch to a sessile lifestyle and start producing a biofilm matrix. The initial steps of in vivo biofilm development are poorly characterized and difficult to assess experimentally. A great amount of in vitro evidence has shown that accumulation of high levels of cyclic dinucleotides (c-di-NMPs) is the most prevalent hallmark governing the initiation of biofilm development by bacteria. As mentioned above, recent studies also link detection of c-di-NMPs by host cells with the activation of a type I interferon immune response against bacterial infections. We discuss here c-di-NMP signaling and the host immune response in the context of the initial steps of in vivo biofilm development.
    No preview · Article · Jun 2013 · Trends in Microbiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Since the introduction of DNA vaccines two decades ago, this attractive strategy has been hampered by its low immunogenicity in humans. Studies conducted to improve the immunogenicity of DNA vaccines have shown that understanding the mechanism of action of DNA vaccines might be the key to successfully improving their immunogenicity. Our current understanding is that DNA vaccines induce innate and adaptive immune responses in two ways: (1) the transfected DNA plasmid itself may bind to an un-identified cytosolic DNA sensor and activate the TBK1-STING pathway and the production of type I interferons (IFNs) which function as an adjuvant; and (2) antigens encoded by DNA plasmids expressed both in stromal cells and dendritic cells (DCs) may lead to the activation/involvement of the STING-TBK1 pathway in antigen presentation via type I IFNs to produce DNA vaccine-induced adaptive immune responses. Recent studies investigating double-stranded cytosolic DNA sensor(s) have highlighted new mechanisms in which cytosolic DNA may release secondary metabolites, which are in turn recognized by a novel DNA sensing machinery. Here, we discuss these new metabolites and the possibilities of translating this knowledge into improved immunogenicity for DNA vaccines.
    Full-text · Article · Aug 2013 · Human Vaccines & Immunotherapeutics
Show more