Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

ABSTRACT: The obligate intracellular pathogen Chlamydia trachomatis is the causative agent of the most common bacterial sexually transmitted disease worldwide. While the host response to infection by this pathogen has been well characterized, it remains unclear to what extent host gene expression during infection is the product of Chlamydia-directed modulation of host transcription factors. In this report, we show the transcriptome of Chlamydia-infected epithelial cells exhibits gene expression consistent with activity of YAP, a transcriptional coactivator implicated in cell proliferation, wound healing, and fibrosis. After confirming induction of YAP target genes during infection, we observed increased YAP nuclear translocation in Chlamydia-infected epithelial cells. We further show that increased YAP activation is a Chlamydia-directed process, requiring de novo protein synthesis during midcycle infection. Surprisingly, infection-mediated YAP activation bypasses YAP inhibition by the Hippo kinase cascade, with phosphorylation at S127 remaining unchanged. Instead, phosphorylation at Y357 was increased along with nuclear translocation, indicating that infection overrides phospho-inhibition at S127. Nuclear translocation of Y357F mutant YAP was not increased by infection, demonstrating that chlamydial YAP activation requires phosphorylation at this residue. Taken together, our results define a transcriptome-altering mechanism potentially linked to chlamydial fibrosis and other advanced disease sequelae.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198272 | GEO | 2023/02/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

Project description:The obligate intracellular pathogen Chlamydia trachomatis is the causative agent of the most common bacterial sexually transmitted disease worldwide. While the host response to infection by this pathogen has been well characterized, it remains unclear to what extent host gene expression during infection is the product of Chlamydia-directed modulation of host transcription factors. In this report, we show the transcriptome of Chlamydia-infected epithelial cells exhibits gene expression consistent with activity of YAP, a transcriptional coactivator implicated in cell proliferation, wound healing, and fibrosis. After confirming induction of YAP target genes during infection, we observed increased YAP nuclear translocation in Chlamydia-infected epithelial cells. We further show that increased YAP activation is a Chlamydia-directed process, requiring de novo protein synthesis during midcycle infection. Surprisingly, infection-mediated YAP activation bypasses YAP inhibition by the Hippo kinase cascade, with phosphorylation at S127 remaining unchanged. Instead, phosphorylation at Y357 was increased along with nuclear translocation, indicating that infection overrides phospho-inhibition at S127. Nuclear translocation of Y357F mutant YAP was not increased by infection, demonstrating that chlamydial YAP activation requires phosphorylation at this residue. Taken together, our results define a transcriptome-altering mechanism potentially linked to chlamydial fibrosis and other advanced disease sequelae.

2023-02-13 | GSE180783 | GEO

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

2023-02-13 | GSE180782 | GEO

Simultaneous transcriptional profiling of bacteria and their host cells by heterogeneous RNA-Seq (hRNA-Seq)

Project description:We developed heterogeneous RNA-Seq (hRNA-Seq) to simultaneously capture prokaryotic and eukaryotic expression profiles of bacteria-infected cells. As proof of principle, hRNA-Seq was applied to Chlamydia-infected cells, successfully obtaining the transcriptomes of both Chlamydia and their host cells at 1 and 24 hours post-infection. Substantial transcription was found in the immediate-early period of infection for both Chlamydia and the host cell. We discovered possible chlamydial immune dampening strategies, and putative positive feedback mechanisms for Chlamydia-induced fibrotic scarring. In summary, hRNA-Seq helps to reveal the complex interplay between invading bacterial pathogens and their host mammalian cells and is immediately applicable to any bacteria/host cell interaction.

2013-12-05 | GSE44253 | GEO

Infection with Chlamydia trachomatis reprograms human cells through inhibition of protein synthesis

Project description:The obligate intracellular bacterium Chlamydia trachomatis replicates in a cytosolic vacuole in human epithelial cells. Infection of human cells with C. trachomatis causes substantial changes to many host cell signalling pathways but the molecular basis of such influence is not well understood. Studies of gene transcription of the infected cell have shown altered transcription of many host cell genes, indicating a transcriptional response of the host cell to the infection. We here describe that infection of human cells with C. trachomatis as well as infection of murine cells with C. muridarum profoundly inhibits protein synthesis of the infected host cell. This inhibition was accompanied by changes to the ribosomal profile of the infected cell indicative of a block of translation initiation, most likely as part of a stress response. The chlamydial protease CPAF also reduced protein synthesis in uninfected cells although CPAF-deficient C. trachomatis showed no defect in this respect. Analysis of polysomal mRNA as a proxy of actively transcribed mRNA identified a number of biological processes differentially affected by chlamydial infection. Mapping of differentially regulated genes onto a protein interaction network identified nodes of up- and down-regulated networks during chlamydial infection. Proteomic analysis of protein synthesis further suggested translational regulation of host cell functions by chlamydial infection. These results demonstrate reprogramming of the host cell during chlamydial infection through the alteration of protein synthesis.

2019-05-21 | GSE114556 | GEO

Early transcriptional landscapes of Chlamydia trachomatis-infected epithelial cells at single cell resolution

Project description:Here we examined host cell gene expression in response to Chlamydia trachomatis infection by applying scRNA-Seq to in vitro C. trachomatis-infected HEp-2 epithelial cells and time-matched uninfected cells over the early chlamydial developmental cycle (3, 6 and 12 hours). We collected 264 single cells across both conditions all time points. The aims of the experiment were examining host cell responses to infection at single cell resolution, and identifying early host cell signatures of infection.

2019-11-19 | GSE132525 | GEO

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

Project description:Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage-Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimicks the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlights the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generate biallelic knockout mutations in the host genes encoding IRF5 and IL-10RA in iPSCs, confirming their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections.

2018-02-14 | PXD005858 | Pride

Chromatin accessibility dynamics of Chlamydia-infected epithelial cells

Project description:We applied Formaldehyde-Assisted Isolation of Regulatory Elements enrichment followed by sequencing (FAIRE-Seq) to generate genome-wide temporal chromatin maps of Chlamydia trachomatis-infected human epithelial cells in vitro over the chlamydial developmental cycle. We detected both conserved and distinct temporal regions of chromatin accessibility associated with C. trachomatis infection. The observed differentially accessible chromatin regions, including several Clusters of Open Regulatory Elements (COREs) and temporally-enriched sets of transcription factors, may help shape the host cell response to infection. These regions and motifs were linked to genomic features and genes associated with immune responses, re-direction of host cell nutrients, intracellular signaling, cell-cell adhesion, extracellular matrix, metabolism and apoptosis. This work will serve as a basis for future functional studies of transcriptional regulation and epigenomic regulatory elements in Chlamydia-infected human cells.

2020-10-28 | GSE132448 | GEO

A Unique insight into the MiRNA profile during Genital Chlamydial Infection

Project description:Genital C. trachomatis (CT) infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is of immense importance in preventing adverse pathology. In this study, we tested the hypothesis that the miRNA profile of a acute primary chlamydial infection characterized by temporary inflammation versus the profile associated with chronic genital chlamydial infections that might precipitate PID or TFI will be different. Thus, we analyzed and compared the differentially expressed miRNAs that regulate CT pathogenesis after a single genital infection and those involved in the development of PID and TFI after repeat infections. Mice (Mus musculus) were infected with Chlamydia muridarum once or twice with a month interval between infections, and then sacrificed and genital tract tissues were collected at 1, 2, 4, and 8 weeks after infection. miRNAs were differentially expressed in both first infection and the re-infection; however, the miRNA expression profile was different for both groups. Pathway analysis showed that, amongst other functions, the differentially regulated miRNA might be regulating several pathways involved in cellular and tissue development, disease conditions and toxicity. Grant number: 1SC2HD086066-03 Funding source: Eunice Kennedy Shriver National Institute of Child Health & Human Development Title: Discovering Novel Biomarkers Predictive of Tubal Infertility Caused by Chlamydia. Principal investigator: Yusuf Omosun Date: 05/01/2015-04/30/2019

2019-01-27 | GSE118396 | GEO

Inhibition of Chlamydia pneumoniae Replication in Human Dendritic cells by TNF-alpha-Induced Indoleamine 2,3-Dioxygenase

Project description:Infection with Chlamydia pneumoniae, a human respiratory pathogen, has been associated with various chronic diseases such as asthma, coronary heart disease and importantly atherosclerosis. Possibly because the pathogen can exist in a persistent form. TNF-a has been reported to induce chlamydial persitence in epithelial cell lines, however the mechanism of TNF-a-induced persistence has not been reported. Moreover, C. pneumoniae persistently infect human dendritic cells (DCs) and activate DCs to produce cytokines including TNF-a. Induction of chlamydial persistence by other cytokines such as IFN-g is known to be due to indoleamine 2,3-dioxygenase (IDO) activity. The present study therefore, investigated whether C. pneumoniae infection can induce IDO activity in dendritic cells, and whether the restriction of chlamydial growth in the DCs by TNF-a is IDO-dependent. Our data indicate that infection of DCs with C. pneumoniae resulted in the induction of IDO expression. Reporting on our use of anti-TNF-a antibody adalimumab and varying concentrations of TNF-a, we further demonstrate that IDO induction following infection of DCs with C. pneumoniae is TNF-a-dependent. The anti-chlamydial activity induced by TNF-a and the expression of chlamydial 16S rRNA gene, euo, groEL1, ftsk and tal genes was correlated with the induction of IDO. Addition of excess amounts of tryptophan to the DC cultures resulted in abrogation of the TNF-a-mediated chlamydial growth restriction. These findings suggest that infection of DCs by C. pneumoniae induces production of functional IDO, which subsequently causes depletion of tryptophan. This may represent a potential mechanism for DCs to restrict bacterial growth in chlamydial infections. Keywords: Chlamydia pneumoniae, Dendritic cells, TNF-a, Indoleamine 2,3-dioxygenase

2009-08-21 | GSE12806 | GEO

Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

Project description:NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.

2022-01-26 | GSE183577 | 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