cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity
Haipeng Liu,Haipeng Liu,Pedro Moura-Alves,Gang Pei,Hans-Joachim Mollenkopf,Robert Hurwitz,Xiangyang Wu,Fei Wang,Siyu Liu,Mingtong Ma,Yiyan Fei,Chenggang Zhu,Anne-Britta Koehler,Dagmar Oberbeck-Mueller,Karin Hahnke,Marion Klemm,Ute Guhlich-Bornhof,Baoxue Ge,Anne Tuukkanen,Michael Kolbe,Anca Dorhoi,Anca Dorhoi,Anca Dorhoi,Stefan H. E. Kaufmann,Stefan H. E. Kaufmann +24 more
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TLDR
Endocytosis facilitates internalization of eCDNs, and the DNA sensor cGAS facilitates sensing of endocytosed CDNs, their perinuclear accumulation, and subsequent STING‐dependent release of type I IFN.Abstract:
Cyclic dinucleotides (CDNs) are important second messenger molecules in prokaryotes and eukaryotes. Within host cells, cytosolic CDNs are detected by STING and alert the host by activating innate immunity characterized by type I interferon (IFN) responses. Extracellular bacteria and dying cells can release CDNs, but sensing of extracellular CDNs (eCDNs) by mammalian cells remains elusive. Here, we report that endocytosis facilitates internalization of eCDNs. The DNA sensor cGAS facilitates sensing of endocytosed CDNs, their perinuclear accumulation, and subsequent STING-dependent release of type I IFN Internalized CDNs bind cGAS directly, leading to its dimerization, and the formation of a cGAS/STING complex, which may activate downstream signaling. Thus, eCDNs comprise microbe- and danger-associated molecular patterns that contribute to host-microbe crosstalk during health and disease.read more
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Molecular mechanisms and cellular functions of cGAS–STING signalling
Karl-Peter Hopfner,Veit Hornung +1 more
TL;DR: The molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling are reviewed, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved.
Journal ArticleDOI
Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity.
Chun Zhou,Xia Chen,Xia Chen,Rosa Planells-Cases,Jiachen Chu,Li Wang,Limin Cao,Zhihong Li,Karen I. López-Cayuqueo,Yadong Xie,Shiwei Ye,Xiang Wang,Florian Ullrich,Shixin Ma,Yiyuan Fang,Xiaoming Zhang,Zhikang Qian,Xiaozheng Liang,Shi Qing Cai,Zhengfan Jiang,Dongming Zhou,Qibin Leng,Tsan Sam Xiao,Ke Lan,Jinbo Yang,Huabin Li,Chao Peng,Zhaozhu Qiu,Thomas J. Jentsch,Hui Xiao +29 more
TL;DR: It is suggested that cell-to-cell transmission of cGAMP via LRRC8/VRAC channels is central to effective anti-viral immunity.
Journal ArticleDOI
Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response.
TL;DR: A comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states is provided.
Journal ArticleDOI
Gasdermin D in macrophages restrains colitis by controlling cGAS-mediated inflammation.
Chunmei Ma,Dongxue Yang,Bingwei Wang,Chunyan Wu,Yuqing Wu,Sheng Li,Xue Liu,Kara Lassen,Lue Dai,Shuo Yang +9 more
TL;DR: It is demonstrated that GSDMD functions in macrophages as a negative regulator to control cyclic GMP–AMP synthase (cGAS)–dependent inflammation, thereby protecting against colitis and the administration of cGAS inhibitor can rescue the colitogenic phenotype in G SDMD-deficient mice.
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