Open AccessJournal Article
DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response (P1375)
Kislay Parvatiyar,Zhiqiang Zhang,Rosane M. B. Teles,Songying Ouyang,Yan Jiang,Zhi-Jie Liu,Shankar S. Iyer,Shivam A. Zaver,Mirjam Schenk,Shang Zeng,Wenwan Zhong,Robert L. Modlin,Yongjun Liu,Genhong Cheng +13 more
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In this article, the authors identify the helicase, DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41) as the pattern recognition receptor (PRR) that senses both cyclic-di-GMP and cyclic -di-AMP.Abstract:
Cytosolic detection of bacterially derived secondary messengers cyclic-di-GMP (c-di-GMP) or cyclic -di-AMP (c-di-AMP) by the host immune system activates an innate immune response characterized by the induction of type I interferons (IFNs) Induction of IFN by c-di-GMP or c-di-AMP has been shown to be dependent on a stimulator of IFN genes-TANK binding kinase 1-IFN regulatory factor 3 (STING-TBK1-IRF3) signaling axis Although STING has been shown to interact with c-di-GMP, an upstream sensor of these cyclic dinucleotides is unknown Here we identify the helicase, DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41) as the pattern recognition receptor (PRR) that senses both c-di-GMP and c-di-AMP DDX41 specifically and directly interacts with c-di-GMP Knockdown of DDX41 via shRNA in murine or human immune cells inhibits the induction of innate immune genes and results in defective STING, TBK1 and IRF3 activation in response to c-di-GMP or c-di-AMP Our findings suggest a mechanism whereby c-di-GMP and c-di-AMP molecules are detected by the DDX41 PRR, which complexes with the STING adaptor to signal to TBK1-IRF3 and activate the IFN responseread more
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Innate immune recognition of DNA: A recent history
Alan Dempsey,Andrew G. Bowie +1 more
TL;DR: The discoveries that led to an appreciation of the existence of cytosolic DNA sensor proteins are reviewed, and two key such sensors, cGAS and IFI16, are discussed in detail.
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Cyclic Dinucleotides and the Innate Immune Response
TL;DR: This Review summarizes recent insights in CDNs and provides a perspective on future unanswered questions in this exciting field and links these two patterns of utilization of CDNs as secondary messengers to each other.
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Interferon regulatory factors: at the crossroads of immunity, metabolism, and disease
TL;DR: An update on the recent progress regarding the regulation of immune responses and immune cell development associated with IRFs is provided and the relationships between IRFs and immunity, metabolism, and disease are discussed, with a particular focus on the role of IRFs as stress sensors.
Journal ArticleDOI
Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants:
TL;DR: Although this relatively new class of adjuvants has to date only been evaluated in mice, newly available CDN-STING cocrystal structures will likely intensify efforts in this field towards further development and evaluation in human trials both in preventive vaccine and immunotherapy settings.
Journal ArticleDOI
Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies
Maya Lewinsohn,Anna L. Brown,Anna L. Brown,Luke M Weinel,Luke M Weinel,Connie Phung,George Rafidi,Ming K. Lee,Andreas W. Schreiber,Andreas W. Schreiber,Jinghua Feng,Milena Babic,Chan-Eng Chong,Young Phil Lee,Agnes S. M. Yong,Graeme Suthers,Graeme Suthers,Nicola K. Poplawski,Nicola K. Poplawski,Meryl Altree,Kerry Phillips,Louise Jaensch,Miriam Fine,Richard J D'Andrea,Richard J D'Andrea,Ian D. Lewis,Bruno C. Medeiros,Daniel A. Pollyea,Mary Claire King,Tom Walsh,Sioban Keel,Akiko Shimamura,Lucy A. Godley,Christopher N. Hahn,Christopher N. Hahn,Jane E. Churpek,Hamish S. Scott +36 more
TL;DR: This study expands both the mutation and phenotypic spectra observed in families with germ line DDX41 mutations, and shows that most asymptomatic mutation carriers have normal blood counts until malignancy develops.
References
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Journal ArticleDOI
Recognition of microorganisms and activation of the immune response.
TL;DR: The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections, and recent progress brings us closer to an integrated view of the immune system and its function in host defence.
Journal ArticleDOI
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
TL;DR: It is shown that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection.
Journal ArticleDOI
Pathogen Recognition by the Innate Immune System
TL;DR: In this review, a comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated byPRRs.
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IFI16 is an innate immune sensor for intracellular DNA.
Leonie Unterholzner,Sinead E. Keating,Marcin Baran,Kristy A. Horan,Søren B. Jensen,Søren B. Jensen,Shrutie Sharma,Cherilyn M. Sirois,Tengchuan Jin,Eicke Latz,Eicke Latz,T. Sam Xiao,Katherine A. Fitzgerald,Søren R. Paludan,Andrew G. Bowie +14 more
TL;DR: IFI16 (p204) is the first PYHIN protein to their knowledge shown to be involved in IFN-β induction and forms a new family of innate DNA sensors the authors call 'AIM2-like receptors' (ALRs).
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Principles of c-di-GMP signalling in bacteria.
TL;DR: This Review focuses on emerging principles of c-di-GMP signalling using selected systems in different bacteria as examples.