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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TLDR
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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Molecular and functional characterization of tilapia DDX41 in IFN regulation
TL;DR: The overexpression of On-DDX41 can elicit a strong activation of both zebrafish IFN1 and IFN3 promoter in fish cells treated with poly(dA:dT) stimulation, and contributes to a better understanding of the functional properties of DDX41 in fish.
Journal ArticleDOI
Porcine IFI16 Negatively Regulates cGAS Signaling Through the Restriction of DNA Binding and Stimulation.
Wanglong Zheng,Zhou Rongyun,Shuangjie Li,He Shan,Jia Luo,Zhu Meiqin,Nanhua Chen,Hongjun Chen,François Meurens,Jianzhong Zhu +9 more
TL;DR: It is found that both enable STING-dependent signaling to downstream IFN upon DNA transfection and HSV-1 infection, and cGAS plays a major role in DNA signaling.
Dissertation
Implication de l’appareil de Golgi et de l’ubiquitination dans l’activation de TBK1 après détection des ARNs viraux
Abstract: L’immunite innee antivirale repose en grande partie sur la production des interferons de type I (IFN-α/β) par les cellules infectees et les cellules immunitaires. Cette synthese resulte de la reconnaissance de motifs viraux caracteristiques par des recepteurs cellulaires, parmi lesquels les RIG-I-Like Recepteurs (RLR) et le Toll-Like Recepteur 3 (TLR3) detectent l’ARN viral respectivement au niveau du cytosol et des endosomes. La signalisation induite par les RLRs et TLR3 conduit a l’activation d’IRF3 et de NF-κB, deux facteurs de transcription impliques respectivement dans la production d’IFN-α/β et de cytokines pro-inflammatoires. TBK1 (TANK-Binding Kinase 1) joue un role essentiel dans l’immunite innee antivirale, de par la phosphorylation du facteur de transcription IRF3, necessaire a la production des IFNs de type I. Bien que de nombreuses etudes aient montre le role crucial de cette kinase dans la signalisation antivirale, le processus entrainant son activation est encore mal determine a ce jour. Lors de cette etude nous avons demontre que suite a la stimulation du TLR3 et des RLRs, la forme active, ubiquitinylee et phosphorylee, de TBK1 se relocalise au niveau de l’appareil de golgi, grâce a son ubiquitination sur les residus K30 et K401. Ce mecanisme implique la reconnaissance des chaines d’ubiquitines associees a TBK1 par l’Optineurine (OPTN), permettant la formation d’un complexe autorisant le rapprochement des molecules de TBK1 puis la trans-autophosphorylation au niveau de l’appareil de Golgi. Au cours de ce travail nous avons egalement decouvert qu’OPTN est la cible d’une proteine virale, la proteine NS3 du BTV (Bluetongue Virus), qui neutralise son activite et diminue ainsi l’activation de TBK1 et la signalisation responsable de la secretion de cytokines antivirales.
Journal ArticleDOI
High-throughput sequencing reveals the gut and lung prokaryotic community profiles of the Chinese giant salamander (Andrias davidianus).
Zhenbing Wu,François-Joël Gatesoupe,Qianqian Zhang,Qianqian Zhang,Xiehao Wang,Yuqing Feng,Shuyi Wang,Dongyue Feng,Aihua Li,Aihua Li +9 more
TL;DR: This study characterized the prokaryotic microbial community profiles in the gut and lung of the Chinese giant salamander, providing foundational support for future study seeking to understand microbiota of the giant Salamander and the role of its microbiota on infectious diseases.
Journal ArticleDOI
A Cytosolic Sensor, PmDDX41, Binds Double Stranded-DNA and Triggers the Activation of an Innate Antiviral Response in the Shrimp Penaeus monodon via the STING-Dependent Signaling Pathway
TL;DR: This study is the first to demonstrate that PmDDX41 acts as a cytosolic DNA sensor that interacts with STING via its DEADc domain to trigger the IFN-β and NF-κB signaling pathways, thus activating antiviral innate immune responses.
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