Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unique transcriptional architecture in airway epithelial cells and macrophages shapes distinct responses following influenza virus infection ex vivo.

ABSTRACT: Airway epithelial cells and macrophages differ markedly in their responses to influenza A virus (IAV) infection. To investigate transcriptional responses underlying these differences, purified subsets of type II airway epithelial cells (ATII) and alveolar macrophages (AM) recovered from the lungs of mock- or IAV-infected mice were subjected to RNA sequencing. In the absence of infection, AM predominantly expressed genes related to immunity whereas ATII expressed genes consistent with their physiological roles in the lung. Following IAV infection, AM almost exclusively activated cell-intrinsic antiviral pathways that were dependent on interferon regulatory factor (IRF)3/7 and/or type I interferon (IFN) signaling. In contrast, IAV-infected ATII activated a broader range of physiological responses, including cell-intrinsic antiviral pathways, which were both independent and dependent on IRF3/7 and/or type I IFN. These data suggest that transcriptional profiles hardwired during development could be a major determinant underlying the different responses of ATII and AM to IAV infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE115904 | GEO | 2018/12/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptomic landscape of murine coronavirus infection in the lung

Project description:Impaired type I interferon (IFN) responses are predictive of severe disease during pulmonary coronavirus infection. Insufficient IFN-responsiveness is associated with viremia and hypercytokinemia, however the resolution of IFN-dependent innate immune responses in the lungs remains limited. Here, we aimed to elucidate the early dynamics of antiviral immunity and define the IFN-dependent mechanisms limiting viral spread during pulmonary infection with the murine coronavirus A59 (M-CoV-A59), a beta-coronavirus. Combining high-resolution transcriptomic analysis and genetic attenuation of interferon signaling, we delineated IFN-dependent cell-intrinsic and population-based transcriptional changes that determined viral replication and inflammatory maturation, respectively.

2023-01-02 | E-MTAB-11781 | biostudies-arrayexpress

Interferon Regulatory Factors: IRF1 and IRF7 directly regulate gene expression in bats in response to viral infection.

Project description:Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with IFNα signalling. Here we show IRF1,3 and 7 levels are elevated in most bat tissues and that basally, IRFs contribute to the expression of type I IFN ligands and high expression of Interferon Regulated Genes (IRGs). CRISPR KO of IRF 1/3/7 in cells reveal distinct subsets of genes affected by each IRF in an IFN-ligand signalling dependent and largely independent manner. As the master regulators of innate immunity, the IRFs, control the kinetics and maintenance of the IRG response and play essential roles in response to IAV, HSV1, PRV3M and MERS-CoV infection. With its differential expression compared to human, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.

2020-10-23 | PXD021982 | JPOST Repository

Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance

Project description:All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at air-liquid interface (ALI). HCoV-229E, HCoV-NL63 and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33ºC) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally-directed IFNs as potential therapeutics.

2024-03-25 | GSE253542 | GEO

IRF1 is a transcriptional regulator of ZBP1 promoting NLRP3 inflammasome activation and cell death during influenza virus infection

Project description:Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms including the NLRP3 inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. Here, we demonstrate the role of interferon regulatory factor 1 (IRF1) in promoting NLRP3 inflammasome activation and cell death during IAV infection. IRF1 functions as a transcriptional regulator of Z-DNA binding protein 1 (ZBP1, also called as DLM1/DAI), a key molecule mediating IAV-induced inflammatory and cell death responses. Therefore, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.

2017-12-07 | GSE103059 | GEO

Differential interferon-α subtype immune signatures suppress SARS-CoV-2 infection

Project description:Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies and have been successfully employed for the treatment of viral diseases. Humans express twelve IFN-alpha (α) subtypes, which activate downstream signalling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in type I IFN immunity and the presence of anti- IFN autoantibodies account for very severe courses of COVID-19, therefore, early administration of type I IFNs may be protective against life-threatening disease. Here we comprehensively analysed the antiviral activity of all IFNα subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate and low antiviral IFNs. In particular IFNα5 showed superior antiviral activity against SARS-CoV-2 infection. Dose-dependency studies further displayed additive effects upon co-administered with the broad antiviral drug remdesivir in cell culture. Transcriptomics of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in type I IFN signalling pathways, negative regulation of viral processes and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multi-modular definition of antiviral host responses mediated by defined type I IFNs. This knowledge shall support the development of novel therapeutic approaches against SARS-CoV-2.

2022-02-09 | PXD026079 | Pride

Differential interferon-α immune signatures prevent SARS-CoV-2 infection

Project description:Type 1 interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control and immune-mediated pathology and have been successfully employed for the treatment of viral diseases. In humans, there are twelve IFN-alpha (α) subtypes, which activate downstream signalling cascades and result in a distinct pattern of immune responses and differential antiviral responses. In this project, we analysed the antiviral activity of IFNα subtypes towards SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Pre-treatment of primary human airway epithelial cells (hAEC) cells with different human IFN-α subtypes demonstrated distinct antiviral activities against SARS-CoV-2. We identified IFNα5 as one of the strongest antiviral acting IFNs against SARS-CoV-2 infection in this study. Dose-dependency studies displayed an additive effect when co-administered with the broad antiviral drug remdesivir in cell culture. Bulk transcriptomics of pre-treated hAEC revealed differentially expressed gene signatures, with IFNα subtype-specific distinct, intersecting and common genes. Proteomic analysis confirmed the expression of distinct interferon effectors for the subset of highly antiviral IFNα5. Therefore, our data elucidate molecular antiviral host responses upon treatment with type I IFNs on several levels, knowledge which could aid in the development of novel therapeutic approaches.

2021-11-28 | GSE189613 | GEO

Genome-wide RNA-seq transcriptional analysis of splenocyte responses to Dengue virus infection in WT, Irf3(-/-)×Irf7(-/-) (DKO), Irf3-/-xIrf5-/-xIrf7-/- (TKO), and Ifnar1-/- (AB6) mice.

Project description:Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that play critical roles in translating viral recognition into antiviral responses, including type I IFN production. Dengue virus (DENV) and other clinically important flaviviruses are controlled by functional type I interferon (IFN) responses. Using an experimental model of DENV infection that recapitulates key aspects of the human disease in mice, we demonstrate that while mice lacking the type I IFN receptor (Ifnar1-/-) succumb to DENV infection, mice that are deficient in IRF-3, IRF-5, and IRF-7 – the three transcription factors thought to regulate type I IFN production – survive DENV challenge. Genome-wide RNA-seq analysis of WT, Irf3(-/-)×Irf7(-/-) (DKO), Irf3-/-xIrf5-/-xIrf7-/- (TKO), and Ifnar1-/- (AB6) splenocytes identified minimal type I IFN production but a robust type II IFN (IFN-γ) response in DKO and TKO mice later shown to be dependent on IRF-1. These results reveal a key role for IRF-1 in antiviral defense by activating both type I and II IFN responses during DENV infection.

2017-11-07 | GSE104189 | GEO

Interferon (IFN)-γ promotes monocyte-mediated lung injury during influenza pathogenesis

Project description:Influenza A Virus (IAV) triggers an exuberant host response that promotes acute lung injury. However, the determinants of the pathological host response to IAV remain incompletely understood. In the current study, we identified interferon (IFN)-γ-regulated subset of monocytes, CCR2+ monocytes, as a driver of lung damage during IAV pathogenesis. IFN-γ regulated the recruitment and inflammatory phenotype of CCR2+ monocytes, and CCR2 (CCR2-/-) and IFN-γ (IFN-γ-/-) deficient mice exhibited reduced lung inflammation, pathology, and increased resistance against bacterial co-infection by Streptococcus pneumoniae (Spn). Adoptive transfer of WT (IFN-γR1+), but not IFN-γR1 deficient (IFN-γR1-) CCR2+ monocytes, restored the wild-type (WT)-like pathological phenotype of lung damage in IAV-infected CCR2-/- mice. The CD8+ T cells were the most significant source of IFN-γ in IAV-infected lungs. Collectively, our data highlight that IFN-γ regulates CCR2+ monocyte-mediated lung pathology during IAV pathogenesis.

2021-11-25 | GSE189407 | GEO

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

Project description:Severe 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 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- 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. Senescent Huh7 cells in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection and SARS-CoV-2 effectively inhibited IFIT1 in these cells. 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. Characterization of the role of different interferon stimulated genes on the inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

2021-05-18 | PXD023450 | Pride

IFN lambda modulates dendritic cells to facilitate T cell immunity during influenza virus infection

Project description:Type I and type III interferon (IFN) are important in regulating responses to viral infection. Type I IFN signaling is know to contribute to dendritic cell (DC) function, but the contribution of type III IFN remains unknown. To determine changes in migratory dendritic cell gene expression during influenza A virus (IAV) in the presence or absence of type I or type III (IFN) receptors, C57Bl/6 (WT) mice, mice lacking the type I IFN receptor (Ifnar-/-), and mice lacking the type III IFN receptor (Ifnlr-/-) were infected intranasally with 40 plaque forming units (PFU) IAV H1N1 strain A/PR/8/34 or mock infected. On day 4, lung-draining lymph nodes (dLN) were harvested, conventional DC were isolated, and mRNA sequencing (mRNAseq) was performed.

2018-12-28 | GSE124399 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data