The cGAS-STING pathway drives type I IFN immunopathology in COVID-19

doi:10.1038/s41586-022-04421-w

. 2022 Mar;603(7899):145-151.

doi: 10.1038/s41586-022-04421-w. Epub 2022 Jan 19.

The cGAS-STING pathway drives type I IFN immunopathology in COVID-19

Jeremy Di Domizio^#¹, Muhammet F Gulen^#², Fanny Saidoune^#¹, Vivek V Thacker^#², Ahmad Yatim^#¹, Kunal Sharma², Théo Nass², Emmanuella Guenova¹, Martin Schaller³, Curdin Conrad¹, Christine Goepfert^{4

5}, Laurence de Leval⁶, Christophe von Garnier⁷, Sabina Berezowska⁶, Anaëlle Dubois⁸, Michel Gilliet⁹, Andrea Ablasser¹⁰

Affiliations

¹ Department of Dermatology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
² Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
³ University Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
⁴ Institute of Animal Pathology, COMPATH, University of Bern, Bern, Switzerland.
⁵ Histology Core Facility, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
⁶ Institute of Pathology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
⁷ Division of Pulmonology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
⁸ Biological Electron Microscopy Facility, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
⁹ Department of Dermatology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland. michel.gilliet@chuv.ch.
¹⁰ Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland. andrea.ablasser@epfl.ch.

^# Contributed equally.

PMID: 35045565
PMCID: PMC8891013
DOI: 10.1038/s41586-022-04421-w

The cGAS-STING pathway drives type I IFN immunopathology in COVID-19

Jeremy Di Domizio et al. Nature. 2022 Mar.

. 2022 Mar;603(7899):145-151.

doi: 10.1038/s41586-022-04421-w. Epub 2022 Jan 19.

Authors

Affiliations

¹ Department of Dermatology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
² Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
³ University Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
⁴ Institute of Animal Pathology, COMPATH, University of Bern, Bern, Switzerland.
⁵ Histology Core Facility, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
⁶ Institute of Pathology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
⁷ Division of Pulmonology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
⁸ Biological Electron Microscopy Facility, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
⁹ Department of Dermatology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland. michel.gilliet@chuv.ch.
¹⁰ Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland. andrea.ablasser@epfl.ch.

^# Contributed equally.

PMID: 35045565
PMCID: PMC8891013
DOI: 10.1038/s41586-022-04421-w

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

A.A. is a scientific co-founder of IFM Due. The other authors declare no competing interests.

Figures

**Fig. 1. Type I IFN-producing macrophages surround damaged endothelial cells in COVID-19 skin lesions.**
a, Immune gene expression profiles of skin lesions from individuals with COVID-19 (n = 10) and individuals with CLE (n = 11), and skin from healthy donors (HD; n = 5). Unbiased clustering was performed. b, Immunohistochemistry quantification of macrophages, neutrophils, plasmacytoid dendritic cells (pDCs) and T cells (stained for CD163, MPO, CD123 and CD3) in CLE (n = 5) and COVID-19 (n = 10) skin lesions. c, Confocal microscopy images of representative COVID-19 skin lesion stained for CD163 (green) and IFNβ (red). Scale bars, 20 μm. d, Contribution of CD163⁺ macrophages and CD31⁺ endothelial cells to IFNβ expression in CLE (n = 5) and COVID-19 (n = 10). e, Confocal microscopy images of representative COVID-19 skin lesion stained for CD31 (green) and IFNβ (red). Scale bars, 20 μm. f, Proportions of CD163⁺ macrophages, CD31⁺ endothelial cells and other cells among IFNβ-producing cells for each CLE and COVID-19 sample. g, Confocal microscopy images of a representative COVID-19 skin sample stained for CD163 (green) and CD31 (red) to depict macrophages and endothelial cells. Scale bar, 50 μm. h, Transmission electron microscopy of dermal vessels in purpuro-necrotic (left) and maculopapular (middle) COVID-19 skin lesions, and in healthy skin (right). Arrows show disrupted endothelial cells (COVID-19 skin lesions) and intact endothelial cells (healthy skin). Scale bars, 2 μm (left); 5 μm (middle); 1 μm (right). i, Immunohistochemistry for cleaved caspase-3 (cl. caspase-3) in COVID-19 skin lesions (nuclear staining indicated by arrow). Scale bar, 20 μm. j, Percentage of CD31⁺ endothelial cells with cleaved caspase-3 staining in healthy skin (n = 8) and in CLE (n = 6) and COVID-19 (n = 10) skin lesions. k, Correlation between cleaved-caspase-3-positive nuclei and overall staining intensity of IFNβ measured in COVID-19 skin samples (n = 8). Spearman correlation and two-tailed statistical significance were performed. Data are mean ± s.d. (b, d, j). P values obtained with two-tailed Student’s t-test and one-way ANOVA followed by Tukey’s multiple comparisons test (b, d, j). Source data

**Fig. 2. cGAS–STING-dependent type I IFN signature in COVID-19 skin and lung pathology.**
a, Confocal microscopy images of a representative COVID-19 skin sample stained for CD163 (green), *IFNB1* mRNA (red) and DNA (blue). Scale bars, 10 μm. Arrows indicate cytosolic DNA particles. b, Quantification of CD163⁺ macrophages containing cytosolic DNA particles in COVID-19 skin lesions (n = 10) and in healthy skin (n = 9). c, Quantification of cGAMP in lysates of COVID-19 skin lesions (n = 10) and healthy skin (n = 3). d, Confocal microscopy images of a representative COVID-19 skin sample stained for CD163 (green) and p-STING (red). Blood vessels, dashed line. Arrows show p-STING⁺ endothelial cells. Scale bars, 20 μm (left); 5 μm (right two images). e, Quantification of p-STING⁺ macrophages in COVID-19 skin lesions (n = 10) and in healthy skin (n = 10). f, Confocal microscopy images of a representative COVID-19 skin sample stained for CD31 (green) and p-STING (red). Blood vessels, dashed line. Scale bars, 20 μm. g, Proportions of CD163⁺ macrophages and CD31⁺ endothelial cells among p-STING⁺ cells in COVID-19 skin lesions (n = 7). h, Expression of ISGs (*IFI35*, *IRF7* and *MX1*) in cultured healthy skin (n = 3) and COVID-19 skin explants (n = 3), treated or not with H-151. i, Confocal microscopy images of representative post-mortem lungs with early (fewer than 10 days; left) or late (more than 14 days, right) DAD, stained for p-STING (red) and CD163 (green). Scale bars (left to right): 20 μm, 10 μm, 50 μm, 10 μm. j, Quantification of p-STING⁺CD163⁺ macrophages in post-mortem lungs with early and late DAD (n = 4). k, Immunohistochemistry of representative post-mortem lungs with early (left) or late (right) DAD, stained for MxA. Scale bar, 50 μm. l, Percentage of tissue area with MxA positivity in early and late DAD samples (n = 4). Data are mean ± s.d. (b, c, e, h, j, l). P values obtained with two-tailed Student’s t-test (c, e, h, j, l) and with Mann–Whitney test (b). Source data

**Fig. 3. STING-dependent type I IFN production and cell death after SARS-CoV-2 infection in endothelial cells.**
a, Schematic of the three-cell component LoC model. b, c, Representative 3D images of the vascular face of uninfected or SARS-CoV-2-infected LoCs with or without vascular H-151 perfusion. ‘3C’, three-cell component (epithelial cells, endothelial cells and macrophages) in b; ‘2C’, two-cell component (epithelial cells and endothelial cells) in c. CD45⁺ macrophage (green), IFNβ (bright pink), cleaved caspase-3 (amber), actin (azure) and nuclear (purple) stainings are shown. Scale bars, 20 μm. d, Representative 3D images of p-STING⁺ endothelial cells (yellow). Scale bars, 20 μm. e, Expression levels of the indicated genes in uninfected (n = 4), infected (n = 5) and H-151-treated (n = 5) LoCs. *CD31* is also known as *PECAM1*. RE, relative expression. f, Representative volumetric electron microscopy images, 3D reconstructions and quantification of the surface-area-to-volume ratio of endothelial cell mitochondria from uninfected (n = 45) and infected (n = 43) LoCs. Solid line, mean; dashed lines, quartiles. Scale bars, 1 μm (left images); grey hexagons (middle images) represent 1 μm³. g, Representative 3D images of the vascular face of infected LoCs with or without vascular VBIT-4 perfusion. Scale bars, 50 μm. Statistics for quantification: b, IFNβ: uninfected (n = 6 fields of view (FOV)), infected (n = 7 FOV) and H-151-treated (n = 4 FOV) LoCs, n = 2 LoCs each; c, IFNβ/cleaved caspase-3: infected (n = 4 FOV in each case) and H-151-treated (n = 4/n = 5 FOV) LoCs, n = 2 LoCs each for both markers; f, data from n = 4 endothelial cells each from n = 1 uninfected and n = 2 infected LoCs; g, IFNβ: infected (n = 7 FOV) and VBIT-4-treated (n = 6 FOV) LoCs, n = 2 LoCs each. Data acquired at 3 dpi; mean ± s.e.m.; P values calculated by one-way ANOVA followed by Tukey’s multiple comparisons tests (b, c, e) or two-tailed Mann–Whitney test (f, g). Source data

**Fig. 4. STING inhibition reduces SARS-CoV-2-induced inflammation in mice.**
a, Schematic of SARS-CoV-2 infection (intranasal; 1 × 10⁴ plaque-forming units (PFU) per mouse) and intraperitoneal administration of vehicle or H-151 (starting at 1 day before infection), related to data from b–d. b, Left, representative haematoxylin and eosin (H&E) images of lungs from vehicle- and H-151-treated mice. Scale bars, 500 μm. Right, average inflamed area in SARS-CoV-2 infected mice. c, mRNA expression levels of the indicated genes in uninfected and infected lungs at 6 dpi, analysed by RT–qPCR. d, Relative weight loss in mice after SARS-CoV-2 infection. e, Schematic of SARS-CoV-2 infection (intranasal; 1 × 10⁴ PFU per mouse) and intraperitoneal administration of vehicle or H-151 (starting at 2 dpi), related to data from f–h. f, Left, representative H&E images of lungs from vehicle- and H-151-treated mice. Scale bars, 500 μm, Right, average inflamed area in SARS-CoV-2 infected mice. g, h, Relative weight loss (g) and survival (h) in mice after SARS-CoV-2 infection with post-infection regimen. Numbers are: a–c, uninfected (n = 4), vehicle and H-151 (n = 7); d, uninfected (n = 8), vehicle and H-151 (n = 12); e–g, uninfected, vehicle and H-151 (n = 5); h, vehicle and H-151 (n = 15). Throughout the figure, data are mean ± s.e.m.; P values calculated by one-way ANOVA followed by Tukey multiple comparison tests (b, c, d, f, g), or by Mantel–Cox survival analysis (h). Mice infected with SARS-CoV-2 were age-matched (12–16 weeks) female K18-hACE2 mice. Source data

**Extended Data Fig. 1. Clinical characteristics of patients with COVID-19 with associated skin manifestations.**
a, Photographs of the skin lesions. b, Clinical parameters and demographics of the 10 patients with COVID-19 selected for this study. HRD, Heart Rhythm Disorder; Overweight (BMI > 25 kg/m², but < 30 kg/m²); COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; DM, diabetes mellitus; AIH, autoimmune hepatitis.

**Extended Data Fig. 2. Immune gene expression profiling of COVID-19 skin lesions and common inflammatory skin diseases.**
a, Immune gene expression profiles of patients with lichen planus (n = 5), cutaneous lupus erythematosus (CLE, n = 10), COVID-19 associated skin lesions (n = 10), plaque-type psoriasis (n = 21), and atopic dermatitis (AD, n = 16) compared to healthy skin (HD, n = 4) assessed by NanoString assay. Differentially expressed genes between different pairwise comparisons (i.e. each disease group vs other skin inflammatory diseases) were used to generate disease-related gene signatures. P value < 0.05, and fold change > 2 were used as cutoffs to choose specific classifiers. b, Volcano plot of upregulated genes in COVID-19 compared with CLE skin lesions. Source data

**Extended Data Fig. 3. Macrophages accumulate around vessels exhibiting prominent endotheliopathy in COVID-19 skin lesions.**
a, Confocal microscopy images of CD3⁺ T cells, CD123⁺ plasmacytoid dendritic cells, MPO⁺ neutrophils, and CD163⁺ macrophages in skin lesions from CLE (top row) and COVID-19 (bottom row). Images are representative of 10 patients with COVID-19 and 5 patients with CLE. b, Percentages of CD163⁺ macrophages present at different distances from blood vessel in COVID-19 skin lesions (n = 9). c, Representative histopathology image of a dermal blood vessel in COVID-19 skin lesions (H&E stain). Blood vessel, dashed line. d, Endothelial cell swelling index, a measure of endotheliopathy, quantified in COVID-19 (n = 10) and CLE skin lesions (n = 6). P values were obtained with one-way ANOVA followed by Tukey’s multiple comparison test (b) and two-tailed Student’s t-test (d). Source data

**Extended Data Fig. 4. Perivascular macrophages engulf dying cells.**
a, b, Confocal microscopy images of representative COVID-19 skin lesion stained for CD163 (green), cleaved caspase-3 (red) and DNA (DAPI). Images are representative of 10 patients with COVID-19. Blood vessel, dashed line.

**Extended Data Fig. 5. Patient characteristics and histopathological analyses of a post-mortem COVID-19-affected lung.**
a, Representative histopathology image of a COVID-19 lung in the early phase of DAD with extensive hyaline membranes (left) or in the late phase of DAD with fibrosis obliterating the alveolar lumina (right) (H&E stain). Arrows indicate hyaline membranes. b, Clinical parameters of the 8 patients with COVID-19 selected for the study. HC, hydroxychloroquine; Phase of the diffuse alveolar damage defined based on pure presence of hyaline membranes (exudative) or fibrotic changes (proliferative); * limit of detection is 20.8 copies per reaction (c/r) for RdRp gene, and 5.4 c/r for E gene; ** spike and nucleocapsid antibody; MxA-staining defined as high (>50% cells with intermediate to strong positive staining), or low (< 50%). c, Confocal microscopy images of representative COVID-19 lung section stained for CD31 (green) and p-STING (red). Arrow indicates an endothelial cell with activated STING. d, Proportions of CD163⁺ macrophages and CD31⁺ endothelial cells among p-STING⁺ cells in COVID-19 lungs (n = 4). Source data

**Extended Data Fig. 6. Responses from distinct cell types after SARS-CoV-2 infection in the LoC system.**
a, mRNA expression levels of SARS-CoV-2 N gene in epithelial and endothelial cells at 3 dpi in 2-cell component LoCs. b, Representative 3D views of the airway surface of a LoC infected with SARS-CoV-2 at 3 dpi. Areas with high levels of IFNβ (bright pink) are shown as surfaces. Macrophage surfaces are depicted in green, and nuclear labelling in purple. c, mRNA expression levels of indicated genes in the epithelial cells at 3 dpi in uninfected (n = 3), infected (n = 5), and H-151-treated (n = 5) 2-cell component LoCs. d, Representative 3D views of the vascular face from uninfected and infected LoCs; PMA-activated WT and *cGAS*^−/− THP-1 cells were added to vascular layer 2 days after infection. LoCs were analysed at 3 dpi by quantifying the total volume with high IFNβ expression/volume with high IFNβ expression within macrophages from uninfected (n = 6/ n = 4 fields of view), infected chips with WT THP-1 cells added (n = 9/ n = 6 fields of view) and infected chips with *cGAS*^−/− THP-1 cells added (n = 6/ n = 5 fields of view) across n = 2 LoCs in each case. e, Representative 3D views of the vascular face from uninfected and infected 3-component LoCs; volumes with high levels of cleaved caspase-3 (amber) are shown as surfaces. Quantification of the total volume with high cleaved caspase-3 expression from uninfected (n = 3 fields of view) and infected (n = 5 fields of view) from n = 1 LoC in each case. ‘3C’ refers to 3-cell component (epithelial cells, endothelial cells, and macrophages) LoCs. Bars represent mean ± s.e.m.; P values were calculated by a two-tailed Mann–Whitney test (a) or one-way ANOVA followed by Tukey’s multiple comparison tests (c, d). Source data

**Extended Data Fig. 7. Effect of innate immune sensors on endothelial cell response after SARS-CoV-2 infection in the LoC model.**
a, Representative images of the epithelial and endothelial cells on LoC infected with SARS-CoV-2 at 3 dpi (above). Western blot characterization of STING expression in epithelial and endothelial cells treated with control (ctrl) and STING shRNAs (below, left). Modal value of CD31 expression in the endothelial layer of LoCs reconstituted with control or STING shRNA treated epithelial or endothelial cells (below, right). Each data point was calculated from a maximum intensity projection of CD31 expression from n = 7 (sh Ctrl - epithelial/sh STING - endothelial), n = 8 (sh Ctrl – epithelial/sh Ctrl – endothelial and sh STING – epithelial/sh Ctrl – endothelial) and n = 9 (sh STING – epithelial/sh STING = endothelial) fields of view from n = 1 LoC in each case. b, Representative 3D views at 3 dpi of the vascular surface of a LoCs reconstituted with endothelial cells treated with ctrl or MAVS shRNA and infected with SARS-CoV-2. Volumes with high levels of IFNβ (bright pink) are shown as surfaces. Quantification of the volume with high IFNβ expression from ctrl (n = 5 fields of view) and MAVS shRNA (n = 4 fields of view) from n = 1 LoC in each case. Reduction of MAVS mRNA in endothelial cells after shRNA transduction (right). ‘2C’ refers to 2-cell component (epithelial cells, endothelial cells) LoCs. Bars represent mean ± s.e.m.; P values were calculated by a one-way ANOVA test followed by Tukey multiple comparison tests (a) or a two-tailed Mann–Whitney test (b). For gel source data, see Supplementary Fig. 1. Source data

**Extended Data Fig. 8. Disruption of mitochondrial homeostasis in endothelial cells after SARS-CoV-2 infection.**
a, Functional interactions between proteins with significantly altered expression identified by a pairwise analysis depicted via an interaction network generated from StringDB and clustered with the MCL algorithm. Functional annotations (GO Biological Processes/ KEGG pathways) relevant to mitochondrial function are indicated. b, Heat map of data from mitochondrial proteins with significantly altered expression identified via a time-course analysis. c, d, Serial block scanning electron microscope image of endothelial cells in LoC system (c) or transmission electron microscopy image of endothelial cells in COVID-19 skin lesion (d). Arrows indicate damaged mitochondria with loss of cristae morphology with a magnified inset at bottom right. As control, arrowhead indicates an intact mitochondrium with a magnified inset at top right. e, Representative 3D views at 3 dpi of the vascular surface of a LoCs reconstituted with endothelial cells treated or untreated with 20 μM ddC for 7 days in total and infected with SARS-CoV-2. Total mtDNA in endothelial cells was quantified by qPCR (right). Volumes with high levels of IFNβ (bright pink) are shown as surfaces. Quantification of the volume with high IFNβ expression from infected (n = 11 fields of view) and ddC treated infected (n = 8 fields of view) from n = 1 and n = 2 LoCs respectively. ‘2C’ refers to 2-cell component (epithelial cells, endothelial cells) LoCs. Bars represent mean ± s.e.m.; P values were calculated by a two-tailed Mann–Whitney test (e). Source data

**Extended Data Fig. 9. Prophylactic STING inhibition reduces pathology and inflammatory gene expression in the late stages of SARS-CoV-2 infection.**
a–d, Mice were infected with SARS-CoV-2 infection (intranasal; 1x10⁴ PFU/mouse) and intraperitoneal administration of vehicle or H-151 was started at 1 day prior to infection. TUNEL assay performed on the infected lung sections collected at 3 or 6 dpi is shown (a). mRNA levels of indicated genes isolated from uninfected and infected mouse lungs at 6 dpi were analysed by RT–qPCR (b). Tissue lysates from the lungs were subjected to Western blotting (c). Viral burden in the lungs and brains was analysed at 6 dpi by plaque assay for infectious virus (d). Numbers are for a and b uninfected (n = 4), day 3 samples (n = 4), day 6 samples (n = 7); for d, uninfected (n = 4) and infected (n = 5). Throughout the figure, bars represent mean ± s.e.m.; P values were calculated by one-way ANOVA followed by Tukey multiple comparison tests. For gel source data, see Supplementary Fig. 1. Source data

**Extended Data Fig. 10. Therapeutic inhibition of STING reduces pathology and inflammatory gene expression after SARS-CoV-2 infection.**
a, b, Mice were infected with SARS-CoV-2 infection (intranasal; 1 × 10⁴ PFU per mouse) and intraperitoneal administration of vehicle or H-151 was started at 2 dpi. mRNA was isolated from uninfected and infected mouse lungs and relative expression of indicated genes were analysed by RT–qPCR (a). Viral burden in the lungs and brains was analysed at 6 dpi by plaque assay for infectious virus (b). c, Model of the involvement of the cGAS–STING pathway in severe SARS-CoV-2 infection created with biorender.com. Numbers are uninfected (n = 4), infected (n = 5) (a, b). Throughout the figure, bars represent mean ± s.e.m.; P values were calculated by one-way ANOVA followed by Tukey multiple comparison tests. Source data

See this image and copyright information in PMC

Comment in

STINGing type I IFN-mediated immunopathology in COVID-19.
Andreakos E. Andreakos E. Nat Immunol. 2022 Apr;23(4):478-480. doi: 10.1038/s41590-022-01174-6. Nat Immunol. 2022. PMID: 35301509 No abstract available.
STING, a critical contributor to SARS-CoV-2 immunopathology.
Li H, Zhou F, Zhang L. Li H, et al. Signal Transduct Target Ther. 2022 Mar 30;7(1):106. doi: 10.1038/s41392-022-00967-3. Signal Transduct Target Ther. 2022. PMID: 35354788 Free PMC article. No abstract available.

Cited by

Aggravating mechanisms from COVID-19.
Lee JH, Sergi C, Kast RE, Kanwar BA, Bourbeau J, Oh S, Sohn MG, Lee CJ, Coleman MD. Lee JH, et al. Virol J. 2024 Sep 27;21(1):228. doi: 10.1186/s12985-024-02506-8. Virol J. 2024. PMID: 39334442 Free PMC article. Review.
A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.
Puray-Chavez M, Eschbach JE, Xia M, LaPak KM, Zhou Q, Jasuja R, Pan J, Xu J, Zhou Z, Mohammed S, Wang Q, Lawson DQ, Djokic S, Hou G, Ding S, Brody SL, Major MB, Goldfarb D, Kutluay SB. Puray-Chavez M, et al. Nat Commun. 2024 Sep 27;15(1):8394. doi: 10.1038/s41467-024-52803-7. Nat Commun. 2024. PMID: 39333139 Free PMC article.
TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.
Zhou R, Wang M, Li X, Liu Y, Yao Y, Wang A, Chen C, Zhang Q, Wu Q, Zhang Q, Neculai D, Xia B, Shao JZ, Feng XH, Liang T, Zou J, Wang X, Xu P. Zhou R, et al. EMBO J. 2024 Sep 20. doi: 10.1038/s44318-024-00244-9. Online ahead of print. EMBO J. 2024. PMID: 39304793
SARS-CoV-2 Nsp15 antagonizes the cGAS-STING-mediated antiviral innate immune responses.
Chiu HP, Yeo YY, Lai TY, Hung CT, Kowdle S, Haas GD, Jiang S, Sun W, Lee B. Chiu HP, et al. bioRxiv [Preprint]. 2024 Sep 5:2024.09.05.611469. doi: 10.1101/2024.09.05.611469. bioRxiv. 2024. PMID: 39282446 Free PMC article. Preprint.
The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.
Cabrera LE, Jokiranta ST, Mäki S, Miettinen S, Kant R, Kareinen L, Sironen T, Pietilä JP, Kantele A, Kekäläinen E, Lindgren H, Mattila P, Kipar A, Vapalahti O, Strandin T. Cabrera LE, et al. PLoS Pathog. 2024 Aug 22;20(8):e1012368. doi: 10.1371/journal.ppat.1012368. eCollection 2024 Aug. PLoS Pathog. 2024. PMID: 39172744 Free PMC article.

See all "Cited by" articles

References

1. Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. - PMC - PubMed
1. Gupta A, et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020;26:1017–1032. - PubMed
1. Lucas C, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584:463–469. - PMC - PubMed
1. Nienhold R, et al. Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat. Commun. 2020;11:5086. - PMC - PubMed
1. Park A, Iwasaki A. Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27:870–878. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- H1 Connect
- The Lens - Patent Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. - PMC - PubMed

[2] Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. - PMC - PubMed

[3] Gupta A, et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020;26:1017–1032. - PubMed

[4] Gupta A, et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020;26:1017–1032. - PubMed

[5] Lucas C, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584:463–469. - PMC - PubMed

[6] Lucas C, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584:463–469. - PMC - PubMed

[7] Nienhold R, et al. Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat. Commun. 2020;11:5086. - PMC - PubMed

[8] Nienhold R, et al. Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat. Commun. 2020;11:5086. - PMC - PubMed

[9] Park A, Iwasaki A. Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27:870–878. - PMC - PubMed

[10] Park A, Iwasaki A. Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27:870–878. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The cGAS-STING pathway drives type I IFN immunopathology in COVID-19

Affiliations

The cGAS-STING pathway drives type I IFN immunopathology in COVID-19

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Research Materials

Miscellaneous