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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Intratumoral STING activations overcome negative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma.
Shohei Harabuchi,Akemi Kosaka,Yuki Yajima,Marino Nagata,Ryusuke Hayashi,Takumi Kumai,Kenzo Ohara,Toshihiro Nagato,Kensuke Oikawa,Mizuho Ohara,Yasuaki Harabuchi,Takayuki Ohkuri,Hiroya Kobayashi +12 more
TL;DR: Findings suggest that the combination therapy using CDDP and an immunomodulating drug like cGAMP would be a rational cancer immunotherapy for patients with HNSCC.
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When STING Meets Viruses: Sensing, Trafficking and Response.
TL;DR: This review is dedicated to the recent advances in the dynamic regulations of STING activation, intracellular trafficking, and post-translational modifications (PTMs) by the host and microbial proteins.
Journal ArticleDOI
Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host.
Maite Echeverz,Begoña García,Amaia Sabalza,Jaione Valle,Toni Gabaldón,Cristina Solano,Iñigo Lasa +6 more
TL;DR: Observations indicate that PGA is an antivirulence factor whose loss may have been a necessary event during Salmonella speciation to permit survival inside the host, since it increased susceptibility to bile salts and oxidative stress, and hindered the capacity of S. Enteritidis to survive inside macrophages and to colonize extraintestinal organs, including the gallbladder.
Journal ArticleDOI
Structural and functional analyses of human DDX41 DEAD domain
Yan Jiang,Yanping Zhu,Weicheng Qiu,Yong-Jun Liu,Genhong Cheng,Zhi-Jie Liu,Zhi-Jie Liu,Songying Ouyang,Songying Ouyang +8 more
TL;DR: The crystal structure of human DDX41, a member of the DEAD-box proteins, containing a disordered N-terminal region, a DEAD domain and a Helicase domain is reported, and it is shown thatDDX41 directly binds DNA and STING via its DEADdomain and triggers activation of signaling mediated by mitogen-activated protein kinases TBK1 and transcription factor IRF3, resulting IFN production.
Journal ArticleDOI
Grouper DDX41 exerts antiviral activity against fish iridovirus and nodavirus infection.
TL;DR: The level of EcDDX41 expression was up-regulated following infection with Singapore grouper iridovirus or red-spotted grouper nervous necrosis virus in grouper spleen (GS) cell cultures, suggesting that Ec DDX41 may be involved in fish virus infection.
References
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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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