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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The emerging roles of the DDX41 protein in immunity and diseases
TL;DR: A review of the recent literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41, as well as its homolog Abstrakt in Drosophila, which is important for survival at all stages throughout the life cycle of the fly.
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Cyclic diguanylate signaling in Gram-positive bacteria.
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Triggering Intracellular Receptors for Vaccine Adjuvantation
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DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.
Carolina Gándara,Juan C. Alonso +1 more
TL;DR: The results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth.
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Myeloid neoplasms with germline DDX41 mutation.
Jesse Cheah,Jesse Cheah,Christopher N. Hahn,Devendra K Hiwase,Devendra K Hiwase,Devendra K Hiwase,Hamish S. Scott,Anna L. Brown,Anna L. Brown +8 more
TL;DR: The various molecular, clinical and biological aspects of myeloid malignancy predisposition due to DDX41 mutation are discussed and how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors are highlighted.
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