scholarly journals Mitotic inactivation of the cGAS‒MITA/STING pathways

2021 ◽  
Author(s):  
Li Zhong ◽  
Hong-Bing Shu
Keyword(s):  
Immune Responses ◽  
Nuclear Membrane ◽  
Innate Immune ◽  
Interferon Response ◽  
Response Factor ◽  
Innate Immune Responses ◽  
Major Pathway ◽  
Mitotic Entry ◽  
Membrane Breakdown ◽  
Cellular Dna

Abstract The cyclic GMP‒AMP synthase (cGAS)‒mediator of interferon response factor 3 activation/stimulator of interferon genes (MITA/STING) axis has emerged as a major pathway, which senses microbial or mis-located cellular DNA in the cytosol to trigger innate immune responses. cGAS senses cytosolic DNA without a preference of self or non-self DNA. How the cGAS‒MITA/STING axis is inactivated upon nuclear membrane breakdown (NEBD) at mitotic entry in vertebrate cells to avoid self DNA sensing remains unclear until very recently. In this review, we summarize the recent advances on how cGAS responds to chromosomes upon NEBD and the mechanisms involved in the inactivation of the cGAS‒MITA/STING pathways in mitosis.

scholarly journals Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Chu ◽  
Chenhui Li ◽  
Yongxing Li ◽  
Qiuya Yu ◽  
Huansha Yu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Therapeutic Benefit ◽  
Perilla Frutescens ◽  
Innate Immune ◽  
Interferon Response ◽  
Innate Immune Responses ◽  
Simplex Virus

Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.

scholarly journals Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xi Chen ◽  
Elisa Saccon ◽  
K. Sofia Appelberg ◽  
Flora Mikaeloff ◽  
Jimmy Esneider Rodriguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Response Type ◽  
Innate Immune Responses ◽  
Interferon Stimulated Genes ◽  
Huh7 Cells ◽  
Related Proteins

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce the susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV, and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon-stimulated genes and their role in the inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

scholarly journals The Specificity of Innate Immune Responses Is Enforced by Repression of Interferon Response Elements by NF- B p50

2011 ◽  
Vol 4 (161) ◽  
pp. ra11-ra11 ◽  
Author(s):  
C. S. Cheng ◽  
K. E. Feldman ◽  
J. Lee ◽  
S. Verma ◽  
D.-B. Huang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Interferon Response ◽  
Innate Immune Responses ◽  
Response Elements

scholarly journals ALG2 regulates type I interferon responses by inhibiting STING trafficking

2021 ◽  
Author(s):  
Wangsheng Ji ◽  
Lianfei Zhang ◽  
Xiaoyu Xu ◽  
Xinqi Liu
Keyword(s):  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Innate Immune Responses ◽  
Downstream Signaling ◽  
Interferon Responses ◽  
Hsv 1

Stimulator of IFN genes (STING), an endoplasmic reticulum (ER) signaling adaptor, is essential for the type I interferon response to cytosolic dsDNA. The translocation from the ER to perinuclear vesicles following binding cGAMP is a critical step for STING to activate downstream signaling molecules, which lead to the production of interferon and pro-inflammatory cytokines. Here we found that apoptosis-linked gene 2 (ALG2) suppressed STING signaling induced by either HSV-1 infection or cGAMP presence. Knockout of ALG2 markedly facilitated the expression of type I interferons upon cGAMP treatment or HSV-1 infection in THP-1 monocytes. Mechanistically, ALG2 associated with the C-terminal tail (CTT) of STING and inhibited its trafficking from ER to perinuclear region. Furthermore, the ability of ALG2 to coordinate calcium was crucial for its regulation of STING trafficking and DNA-induced innate immune responses. This work suggests that ALG2 is involved in DNA-induced innate immune responses by regulating STING trafficking.

scholarly journals Pseudomonas aeruginosa Suppresses Interferon Response to Rhinovirus Infection in Cystic Fibrosis but Not in Normal Bronchial Epithelial Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 4131-4145 ◽  
Author(s):  
Sangbrita S. Chattoraj ◽  
Shyamala Ganesan ◽  
Andrea Faris ◽  
Adam Comstock ◽  
Wai-Ming Lee ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Interferon Response ◽  
Innate Immune Responses ◽  
Normal Cells ◽  
Bronchial Epithelial ◽  
Content Type ◽  
Infected Cells

ABSTRACTDespite increased morbidity associated with secondary respiratory viral infections in cystic fibrosis (CF) patients with chronicPseudomonas aeruginosainfection, the underlying mechanisms are not well understood. Here, we investigated the effect ofP. aeruginosainfection on the innate immune responses of bronchial epithelial cells to rhinovirus (RV) infection. CF cells sequentially infected with mucoidP. aeruginosa(MPA) and RV showed lower levels of interferons (IFNs) and higher viral loads than those of RV-infected cells. Unlike results for CF cells, normal bronchial epithelial cells coinfected with MPA/RV showed higher IFN expression than RV-infected cells. In both CF and normal cells, the RV-stimulated IFN response requires phosphorylation of Akt and interferon response factor 3 (IRF3). Preinfection with MPA inhibited RV-stimulated Akt phosphorylation and decreased IRF3 phosphorylation in CF cells but not in normal cells. Compared to normal, unstimulated CF cells or normal cells treated with CFTR inhibitor showed increased reactive oxygen species (ROS) production. Treatment of CF cells with antioxidants prior to MPA infection partially reversed the suppressive effect of MPA on the RV-stimulated IFN response. Together, these results suggest that MPA preinfection inhibits viral clearance by suppressing the antiviral response particularly in CF cells but not in normal cells. Further, increased oxidative stress in CF cells appears to modulate the innate immune responses to coinfection.

scholarly journals Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

2021 ◽  
Author(s):  
Xi Chen ◽  
Elisa Saccon ◽  
K. Sofia Appelberg ◽  
Flora Mikaeloff ◽  
Jimmy Esneider Rodriguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Response Type ◽  
Innate Immune Responses ◽  
Interferon Stimulated Genes ◽  
Huh7 Cells ◽  
Related Proteins

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon stimulated genes and their role in inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

Innate immune responses and type 1 diabetes: A role for a long non-coding RNA?

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
MP Ashton ◽  
I Tan ◽  
L Mackin ◽  
C Elso ◽  
E Chu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Non Coding Rna ◽  
Long Non Coding Rna
Sign in / Sign up

Export Citation Format

Share Document