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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Conservation of the STING-Mediated Cytosolic DNA Sensing Pathway in Zebrafish
TL;DR: The zebrafish larva is established as a useful model for studying HSV-1 infection and represents an amenable model for the investigation of cytosolic DNA sensing mechanisms, shedding light on the conservation of the STING antiviral signaling pathway.
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Radiation-sensitive gene A (RadA) targets DisA, DNA integrity scanning protein A, to negatively affect cyclic Di-AMP synthesis activity in Mycobacterium smegmatis.
Lei Zhang,Zheng-Guo He +1 more
TL;DR: A novel mechanism of control of c-di-AMP synthesis and its effects on bacterial growth in Mycobacterium smegmatis is reported and it is shown that the interaction between RadA and DisA and its role in inhibiting c- DiAMP synthesis may be conserved in bacteria.
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Staphylococcus aureus modulation of innate immune responses through Toll-like (TLR), (NOD)-like (NLR) and C-type lectin (CLR) receptors
TL;DR: This review summarizes recent findings on the various mechanisms applied by S. aureus to modulate or interfere with inflammatory responses through PRRs to provide new insights toward future immune-stimulatory therapeutics against infection or immunomodulatory therapies to suppress or correct dysregulated inflammation.
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Nucleic acid recognition orchestrates the anti-viral response to retroviruses
TL;DR: It is shown that APOBec3 limits the levels of reverse transcripts that trigger cytosolic sensing, and that nucleic acid sensing in vivo increases expression of IFN-regulated restriction factors like APOBEC3 that in turn reduce viral load.
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A decade of research on the second messenger c-di-AMP
TL;DR: The key role of c-di-AMP in maintaining bacterial osmotic balance, especially in Gram-positive bacteria is emphasized, and the future directions and trends of the c- Di-AMP regulatory network are discussed, such as the likely existence of potential c-Di-AMP transporter(s), the possibility of crosstalk between c- di-AMP signaling with other regulatory systems, andThe effects of c
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