Primary mesenchymal cells from the human fallopian tube infected with Chlamydia trachomatis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109428 | GEO | 2023/01/31
REPOSITORIES: GEO
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Project description:Chronic infections of the Fallopian tubes with Chlamydia trachomatis (Ctr) can cause scarring and inflammation and can lead to infertility. Here we describe a model of human fallopian tube organoids for chronic Ctr infection. Interestingly, the normal human cells respond to infection with an active expulsion of the bacteria from the apical side of the epithelium and compensatory cellular proliferation clearly demonstrating a role of epithelial homeostasis in the defense against this infectious agent. Upon progression of the infected culture for over 9 months, the population of epithelial cells underwent a permanent shift towards a less differentiated state. LIF signaling is an essential feature, regulating stemness in the tube and organoid formation, and is activated in response to Ctr. Hallmarks of an organoid infection include a relative increase of secretory cells, expansion of the CD24+ positive population, upregulation of SPP1 factor, as well as downregulation of HOXA4 and HOXA5 homeobox genes. Moreover, Ctr increases hypermethylation of DNA in polycomb repressed genomic regions, an indicator of accelerated molecular aging. This infection model reveals an intriguing link between Ctr and regulation of the host epigenome and suggests that this pathogen has a long-term impact on the interaction of the epithelium with the microenviroment. These permanent changes in the epithelium may be a contributing factor in the development of tubal pathologies, including the development of high grade serous ovarian cancer (HGSOC).
2019-01-31 | GSE108202 | GEO
Project description:Chronic Chlamydia trachomatis infection of fallopian tube organoids
| PRJNA422811 | ENA
Project description: Not available
| S-EPMC7440757 | biostudies-literature
Project description: Not available
| S-EPMC6434919 | biostudies-literature
Project description:Chlamydia trachomatis is the causative agent of sexually transmitted disease with the highest prevalence in the world today. Although, sensitive to antibiotic treatment, Ctr is also a major cause of infertility due to significant cell damage caused to the genital tract of affected women. Occlusion of Fallopian tubes is a frequent consequence of advanced ascending Ctr infection. So far the mechanisms of Ctr caused pathogensis are widely unclear. Here we show, by using an ex vivo infection model of human Fallopian tubes that Ctr causes changes in epithelial homeostasis within 2 days of inoculation, by disrupting cell adhesion and increasing cell proliferation. We demonstrate by imaging and expression analysis that tissue response to invading pathogen has also a paracrine component. We identify Wnt signalling activation as one of the hallmarks of Ctr infection which transmits effects of the infection beyond inclusion containing cells. Mechanisms of phenotypic changes involve up regulation of Epcam and Olfactomedin 4, biomarkers and regulators of cell adhesion and cell differentiation. Our findings bring focus to the pleiotropic effects of Ctr infection within epithelium and could be provide the basis for better understanding the pathological sequels in vivo. Microarray experiments were performed as dual-color hybridizations. To compensate for dye-specific effects, an independent dye-reversal color-swap was applied. Quality control and quantification of total RNA amount was assessed using an Agilent 2100 bioanalyzer (Agilent Technologies) and a NanoDrop 1000 spectrophotometer (Kisker).
2011-11-21 | E-GEOD-26692 | biostudies-arrayexpress
Project description:Chlamydia trachomatis is the causative agent of sexually transmitted disease with the highest prevalence in the world today. Although, sensitive to antibiotic treatment, Ctr is also a major cause of infertility due to significant cell damage caused to the genital tract of affected women. Occlusion of Fallopian tubes is a frequent consequence of advanced ascending Ctr infection. So far the mechanisms of Ctr caused pathogensis are widely unclear. Here we show, by using an ex vivo infection model of human Fallopian tubes that Ctr causes changes in epithelial homeostasis within 2 days of inoculation, by disrupting cell adhesion and increasing cell proliferation. We demonstrate by imaging and expression analysis that tissue response to invading pathogen has also a paracrine component. We identify Wnt signalling activation as one of the hallmarks of Ctr infection which transmits effects of the infection beyond inclusion containing cells. Mechanisms of phenotypic changes involve up regulation of Epcam and Olfactomedin 4, biomarkers and regulators of cell adhesion and cell differentiation. Our findings bring focus to the pleiotropic effects of Ctr infection within epithelium and could be provide the basis for better understanding the pathological sequels in vivo.
2011-11-21 | GSE26692 | GEO
Project description:The prevalence of trachomatous inflammation–follicular (TF) in Solomon Island children aged 1–9 years is high enough to warrant, among other interventions, mass distribution of azithromycin. However, over 90% of those with TF did not have concurrent Chlamydia trachomatis infection. We analysed the transcriptome of children with TF and Ct infection, children diagnosed with TF but no Ct infection and children with neither TF nor Ct infection to better understand host responses during an episode of TF, and investigate whether it can provide any clues about the aetiology of TF in this context.
2018-02-28 | GSE106961 | GEO
Project description:Chlamydia trachomatis (Ctr) is able to colonize the human fallopian tube, causing scarring and inflammation, which can lead to infertility. Here we describe a chronic Ctr infection model using human fallopian tube organoids. The defense response of the organoids to infection includes active expulsion of the bacteria from the apical side of the epithelium and compensatory cellular proliferation, clearly demonstrating a role for core mechanisms of epithelial homeostasis in defense against this invading pathogen. During progression in culture for over 9 months, the population of epithelial cells underwent a permanent shift towards a more dedifferentiated state. We identify LIF signaling an essential for regulation of the stemness in the tube and formation of organoids, and report its activation triggered by Ctr . In the long term, chronic Ctr infection leads to changes in the composition of the epithelium, marked by an increase in the proportion of secretory cells, expansion of the CD24+ positive population, upregulation of SPP1 factor, as well as downregulation of inflammatory mediators CD90, CD83, and CCR7. Ctr increases hypermethylation of DNA in polycomb repressed genomic regions - indicator of accelerated molecular aging. This infection model reveals an important link between Ctr and regulation of the host epigenome and suggests that Ctr has a long-term impact on the epithelial interaction with the immune system. These permanent changes in the epithelium may be a contributing factor in the development of tubal pathologies, particularly development of high grade serous ovarian cancer (HGSOC).
2019-01-31 | GSE107712 | GEO
Project description:The aim of this study was to perform a microarray analysis of the response pattern of EEC from both large and small bowel to infection in vitro, using Chlamydia trachomatis infection as a model. Two human EEC lines: LCC-18, derived from a neuroendocrine colonic tumour, and CNDT-2, derived from a small intestinal carcinoid, were infected with C. trachomatis serovar LGV II strain 434 (ATCC VR-902B). Penicillin G was used to induce persistent infection. Gene expression levels in infected and persistently infected EEC cells were investigated by microarray analysis
2014-06-03 | E-GEOD-58151 | biostudies-arrayexpress
Project description:Introduction Chlamydia trachomatis (C. trachomatis) is a Gram-negative bacterium and a common human pathogen. The World Health Organization (WHO) estimates that over 130 million people are infected with C. trachomatis globally each year and with increasing incidence. C. trachomatis causes long-lasting and recurrent infections that over time induce severe tissue damage in the female genital tract that can lead to ectopic pregnancy and infertility. Thus, the human immune system fails to control and eradicate C. trachomatis during primary infection and fails to develop protective immunity against secondary infections. In vivo infection models, using complement knock out mice, suggest that the complement system is critically involved in both anti-chlamydial immunity and infection-induced pathology. To increase our understanding of complement-mediated immunity against C. trachomatis we analyzed global complement deposition on serum-incubated C. trachomatis by mass spectrometry. Methods Purified C. trachomatis was incubated in seronegative normal human serum (NHS) or heat-inactivated normal human serum (HI-NHS) for 30 min, thoroughly washed, and processed for mass spectrometry. All samples were lysed, reduced and alkylated and digested with trypsin. Some samples were chemically modified to acetylate free amino groups (N-terminal and lysine amino groups) before trypsin digestion. Peptides were analyzed on a UltimateTM 3500 RSLCnano coupled to a Q Exactive HF-X mass spectrometer. Raw data files were searched against the Uniprot human reference proteome using MaxQuant. Results We demonstrate that C. trachomatis elicits potent complement activation demonstrated by deposition of both early and late complement factors together with several complement regulators. We further demonstrate proteolytically processing of complement C3b to “inactive” C3 cleavage fragments. Conclusion We demonstrate the deposition of several novel complement-associated proteins and -cleavage fragments on the surface of C. trachomatis.
2020-11-23 | PXD019393 | Pride