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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Biofilm formation – what we can learn from recent developments
Thomas Bjarnsholt,Thomas Bjarnsholt,Kåre Buhlin,Yves F. Dufrêne,Mark Gomelsky,Anna Moroni,Madeleine Ramstedt,Kendra P. Rumbaugh,Tim Schulte,Tim Schulte,L. Sun,B. Åkerlund,Ute Römling +12 more
TL;DR: In this work, basic studies of biofilm physiology have resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors, which open up new venues for exploring novel anti‐biofilm strategies.
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Mechanisms of Immune Tolerance in Leukemia and Lymphoma
TL;DR: The mechanisms through which immune responses are generated against solid cancers are well characterized and knowledge of the immune evasion pathways exploited by these malignancies has grown considerably but the pathways that regulate immune activation or tolerance are less clear.
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STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice.
TL;DR: It is demonstrated that peptides representing CD8 T cell epitopes can be effective inducers of large CD 8 T cell responses in vaccination strategies that mimic acute viral infections.
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Inhibition of innate immune cytosolic surveillance by an M. tuberculosis phosphodiesterase
Ruchi Jain Dey,Ruchi Jain Dey,Bappaditya Dey,Bappaditya Dey,Bappaditya Dey,Yue Zheng,Yue Zheng,Yue Zheng,Laurene S. Cheung,Jie Zhou,Jie Zhou,David A. Sayre,Pankaj Kumar,Haidan Guo,Gyanu Lamichhane,Herman O. Sintim,Herman O. Sintim,William R. Bishai,William R. Bishai +18 more
TL;DR: Findings reveal a crucial role of CDN homeostasis in governing the outcome of M. tuberculosis infection as well as a unique mechanism of subversion of the host's cytosolic surveillance pathway (CSP) by a bacterial PDE that may serve as an attractive antimicrobial target.
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Crosstalk between Mycobacterium tuberculosis and the host cell.
TL;DR: Several mechanisms to evade the human immune system at multiple levels are described, with an emphasis on the cyclic nucleotide signaling and subversion of host responses that occur at the intracellular level when tubercle bacilli encounter macrophages.
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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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TL;DR: This Review focuses on emerging principles of c-di-GMP signalling using selected systems in different bacteria as examples.