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10.1038/s41586-022-04421-w http://scihub22266oqcxt.onion/10.1038/s41586-022-04421-w 35045565!8891013!35045565     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2022 ; 603 (7899): 145-151 Nephropedia Template TP {{tp|p=35045565|t=2022. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 |pdf=|usr=}}{{35045565}} gab.com Text The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=35045565 #FOAvip COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications(1,2). Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs (3-5)). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome(5-17). Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. (18)). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature that is primarily mediated by macrophages adjacent to areas of endothelial cell damage. Moreover, cGAS-STING activity was detected in lung samples from patients with COVID-19 with prominent tissue destruction, and was associated with type I IFN responses. A lung-on-chip model revealed that, in addition to macrophages, infection with SARS-CoV-2 activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, which leads to cell death and type I IFN production. In mice, pharmacological inhibition of STING reduces severe lung inflammation induced by SARS-CoV-2 and improves disease outcome. Collectively, our study establishes a mechanistic basis of pathological type I IFN responses in COVID-19 and reveals a principle for the development of host-directed therapeutics. Twit Text FOAVip The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=35045565 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35045565 #FOAvip English Wikipedia <ref>{{Cite pmid|35045565}}</ref> The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 #MMPMID35045565 Domizio JD; Gulen MF; Saidoune F; Thacker VV; Yatim A; Sharma K; Nass T; Guenova E; Schaller M; Conrad C; Goepfert C; de Leval L; Garnier CV; Berezowska S; Dubois A; Gilliet M; Ablasser A Nature 2022[Mar]; 603 (7899): 145-151 PMID35045565show ga COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications(1,2). Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs (3-5)). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome(5-17). Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. (18)). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature that is primarily mediated by macrophages adjacent to areas of endothelial cell damage. Moreover, cGAS-STING activity was detected in lung samples from patients with COVID-19 with prominent tissue destruction, and was associated with type I IFN responses. A lung-on-chip model revealed that, in addition to macrophages, infection with SARS-CoV-2 activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, which leads to cell death and type I IFN production. In mice, pharmacological inhibition of STING reduces severe lung inflammation induced by SARS-CoV-2 and improves disease outcome. Collectively, our study establishes a mechanistic basis of pathological type I IFN responses in COVID-19 and reveals a principle for the development of host-directed therapeutics. |Animals[MESH] |COVID-19/*immunology/metabolism/*pathology/virology[MESH] |Cells, Cultured[MESH] |DNA, Mitochondrial/metabolism[MESH] |Disease Models, Animal[MESH] |Disease Progression[MESH] |Endothelial Cells/pathology[MESH] |Female[MESH] |Gene Expression Regulation/immunology[MESH] |Humans[MESH] |Immunity, Innate[MESH] |Interferon Type I/*immunology[MESH] |Lung/immunology/metabolism/pathology/virology[MESH] |Macrophages/immunology[MESH] |Membrane Proteins/antagonists & inhibitors/*metabolism[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Nucleotidyltransferases/*metabolism[MESH] |Pneumonia/immunology/metabolism/pathology/virology[MESH] |SARS-CoV-2/*immunology/pathogenicity[MESH] |Signal Transduction[MESH]The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 (epmc).pdf DeepDyve Pubget Overpricing