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 cytosolic sensor, DDX41, activates antiviral and inflammatory immunity in response to stimulation with double-stranded DNA adherent cells of the olive flounder, Paralichthys olivaceus.
Nhu Truong Quynh,Jun-ichi Hikima,Young Rim Kim,Fernand F. Fagutao,Mee Sun Kim,Takashi Aoki,Tae Sung Jung +6 more
TL;DR: The results suggest that DDX41 functions as a cytosolic DNA sensor that is capable of inducing antiviral activity and inflammatory responses in the olive flounder.
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Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity
TL;DR: It is shown that c-di-GMP can directly target the human LCN2 protein to inhibit its antibacterial activity and can significantly reduceLCN2-mediated inhibition on the in vitro growth of Escherichia coli.
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The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity.
Pengyan Xia,Shuo Wang,Zhen Xiong,Xiaoxiao Zhu,Buqing Ye,Ying Du,Shu Meng,Yuan Qu,Jing Liu,Guangxia Gao,Yong Tian,Zusen Fan +11 more
TL;DR: The ER-associated protein ERAdP is shown to be a high-affinity receptor for c-di-AMP, linking it to downstream inflammatory responses in innate immune cells, critical for controlling bacterial infection.
Journal ArticleDOI
Biofilm switch and immune response determinants at early stages of infection
TL;DR: In this paper, the authors discuss the role of cyclic dinucleotides (c-di-NMPs) signaling and the host immune response in the context of the initial steps of in vivo biofilm development.
Journal ArticleDOI
Innate sensing of bacterial cyclic dinucleotides: more than just STING.
TL;DR: Bacterial cyclic dinucleotides are recognized by the innate immune system, and this leads to the induction of type I interferons, and the mammalian helicase DDX41 directly bindscyclic din nucleotides and mediates the signaling pathway to the induction of type II interferon.
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