Unique expression profile for type-I, -II, and -III IFNs regarding epithelial reorganization in primary epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209727 | GEO | 2022/12/08
REPOSITORIES: GEO
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Project description:Unique expression profile for type-I, -II, and -III IFNs regarding epithelial reorganization in primary epithelial cells
| PRJNA862162 | ENA
Project description:Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. Samples were treated with IFN or IL28b after 6 or 24 hours with three replications
2012-03-09 | E-GEOD-31193 | biostudies-arrayexpress
Project description:Type III IFNs (IFN-λs) are secreted factors that are well-known for their antiviral activities. However, their regulation and functions during bacterial infections are unclear. In this article, we report that the regulation of IFN-λ genes did not track with mechanisms that control type I IFN expression in response to TLRs. Whereas type I IFNs were only expressed from TLRs present on endosomes, type III IFNs could be induced by TLRs that reside at the plasma membrane and that detect various bacterial products. The mechanisms that regulate type III IFN gene expression tracked with those that promote inflammatory cytokine and chemokine expression. Importantly, rIFN-λs enhanced epithelial barriers in vitro, preventing transcellular bacteria dissemination. We therefore propose that in addition to their functions in cell-intrinsic antiviral immunity, type III IFNs protect epithelial barrier integrity, an activity that would benefit the host during any infectious encounter.
| S-EPMC5679450 | biostudies-literature
Project description:To analyze the transcriptome changes of differentiating monocytes in response to type I IFNs, RNA seq was performed. The MACS-purified mouse BM monocytes were cultured in the presence or absence of I IFNs for 12 h or 24h under the condition of M-CSF, samples were harvested for total RNAs and subjected to RNA sequencing analyses.
2022-12-31 | GSE192418 | GEO
Project description:We provide the first comprehensive analysis of nasal cell responses to SARS-COV-2 using single cell transcriptomics and proteomics. The immune response to SARS-CoV-2 is dominated by a delayed type I and III IFN response, which is too slow to contain viral replication. Cells transitioning from secretory to ciliated states are highly permissive to SARS-CoV-2, whereas goblet cells are relatively resistant. Cell-type differences in the production and response to IFN-I/III correlate with permissiveness. Pre-treatment with recombinant IFNs potently restricts SARS-CoV-2. Nasal delivery of recombinant IFNs is a promising prophylactic strategy for SARS-CoV-2
2021-05-25 | PXD022523 | Pride
Project description:Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders.
2012-03-09 | GSE31193 | GEO
Project description:The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens – and especially intracellular bacteria – by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
2021-01-19 | GSE165020 | GEO
Project description:The innate defense mechanisms that control infections with intracellular bacteria are still incompletely understood. Here we show that type I and II IFNs are key regulators of the early gene expression and the host-protective immune response during Legionella pneumophila-induced pneumonia. Using mixed bone marrow-chimeric mice and isolated cells we indicate that both IFNs protect against L. pneumophila by activating an alveolar macrophage-intrinsic antibacterial defense pathway. Quantitative mass spectrometry analysis reveals that both IFNs markedly alter the protein composition of purified Legionella-containing vacuoles, and integrated network analysis defines distinct subsets of IFN-regulated proteins. Subsequent experiments uncover Immunoresponsive gene 1 (Irg1) as a central effector that restricts the bacteria through production of itaconic acid. Collectively, we provide a comprehensive analysis of IFN-mediated effects on gene expression and the bacterial vacuole proteome, and show that L. pneumophila is restricted by an Irg1-dependent production of a bactericidal metabolite. Microarray experiments were performed as dual-color hybridizations on Agilent mouse whole genome catalog 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.
2015-01-01 | E-GEOD-60085 | biostudies-arrayexpress
Project description:The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies. hepatocellular carcinoma cell lines HCC-1.2 and HCC-1.1 cells, referred to as 3p and 3sp cells, respectively, were isolated from one HCC patient as described ( Sagmeister S, Eisenbauer M, Pirker C, et al. New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis. Br J Cancer 2008;99(1):151-9.). 3p cells of passages 10 to 12 and 3sp cells of passages 7 to 13 are termed 3p early and 3sp early, respectively. 3p cells between passage 71 and 76 and 3sp from passage 72 to 87 were termed 3p late and 3sp late, respectively
2011-11-21 | E-GEOD-26391 | biostudies-arrayexpress
Project description:The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies.
2011-11-21 | GSE26391 | GEO