Chlamydia Trachomatis Infection: Their potential implication in the Etiology of Cervical Cancer.
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ABSTRACT:
SUBMITTER: Yang X
PROVIDER: S-EPMC8247366 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In the female genital ecosystem, the complex interplay between the host immune system and the resident microflora protects against urogenital pathogens, like Chlamydia trachomatisC. trachomatis is responsible for urethritis and cervicitis; however, most chlamydial infections are asymptomatic and, thus, not treated, potentially leading to severe reproductive sequelae. Here we investigated the interaction between the levels of selected immune mediators and the community state types of the cervical microbiota in C. trachomatis-infected women. Cervical samples from 42 C. trachomatis-positive women and 103 matched healthy controls were analyzed through the metagenomic analysis of the hypervariable region v4 of the 16S rRNA gene and the determination of lactoferrin, interleukin 1α (IL-1α), IL-6, alpha interferon (IFN-α), IFN-β, and IFN-γ by ELISA. Overall, C. trachomatis infection was significantly associated with a microbiota dominated by anaerobic bacteria (P = 0.000002). In addition, a network of Gardnerella vaginalis, Prevotella amnii, Prevotella buccalis, Prevotella timonensis, Aerococcus christensenii, and Variovorax guangxiensis has been identified as a potential biomarker of C. trachomatis infection through multiple statistical approaches. Again, chlamydial infection was significantly correlated with an increased production of lactoferrin, IL-6, IL-1α, IFN-α, and IFN-β (P < 0.05), whereas very low levels of IFN-γ were observed in C. trachomatis-infected women, levels similar to those detected in healthy women. Our findings show a distinctive signature of C. trachomatis genital infection, characterized by a specific bacterial network, constituted by anaerobes, as well as by increased levels of lactoferrin and proinflammatory cytokines (IL-1α, IL-6, IFN-α, and IFN-β), accompanied by low levels of IFN-γ.IMPORTANCE To our knowledge, this is the first study that investigated the association of C. trachomatis with the cervical levels of lactoferrin and selected inflammatory mediators and their correlation with the different community state types characterizing the female genital ecosystem. C. trachomatis, known as the leading cause of bacterial sexually transmitted diseases, continues to be an important public health problem worldwide for its increasing incidence and the risk of developing severe reproductive sequelae, like pelvic inflammatory disease and infertility. Specifically, C. trachomatis tend to persist in the female genital tract, leading to a chronic inflammatory state characterized by increased production of immune mediators responsible for tissue damage. Therefore, our study may help to broaden the knowledge on the complex interplay between the female genital microbiota and the host immune system in response to C. trachomatis infection.
| S-EPMC6550367 | biostudies-literature
Project description:Pannexin 1 (Panx1) is a plasma membrane channel glycoprotein that plays a role in innate immune response through association with the inflammasome complex. Probenecid, a classic pharmacological agent for gout, has also been used historically in combination therapy with antibiotics to prevent cellular drug efflux and has been reported to inhibit Panx1. As the inflammasome has been implicated in the progression of Chlamydia infections, and with chlamydial infections at record levels in the US, we therefore investigated whether probenecid would have a direct effect on Chlamydia trachomatis development through inhibition of Panx1. We found chlamydial development to be inhibited in a dose-dependent, yet reversible manner in the presence of probenecid. Drug treatment induced an aberrant chlamydial morphology consistent with persistent bodies. Although Panx1 was shown to localize to the chlamydial inclusion, no difference was seen in chlamydial development during infection of cells derived from wild-type and Panx1 knockout mice. Therefore, probenecid may inhibit C. trachomatis growth by an as yet unresolved mechanism.
| S-EPMC3659042 | biostudies-literature
Project description:Chlamydia trachomatis genital infection continues to be an important public health problem worldwide due to its increasing incidence. C. trachomatis infection can lead to severe sequelae, such as pelvic inflammatory disease, obstructive infertility, and preterm birth. Recently, it has been suggested that the cervico-vaginal microbiota may be an important defense factor toward C. trachomatis infection as well as the development of chronic sequelae. Therefore, the investigation of microbial profiles associated to chlamydial infection is of the utmost importance. Here we present a pilot study aiming to characterize, through the metagenomic analysis of sequenced 16s rRNA gene amplicons, the cervical microbiota from reproductive age women positive to C. trachomatis infection. The main finding of our study showed a marked increase in bacterial diversity in asymptomatic C. trachomatis positive women as compared to healthy controls in terms of Shannon's diversity and Shannon's evenness (P = 0.031 and P = 0.026, respectively). More importantly, the cervical microbiota from C. trachomatis positive women and from healthy controls significantly separated into two clusters in the weighted UniFrac analysis (P = 0.0027), suggesting that differences between the two groups depended entirely on the relative abundance of bacterial taxa rather than on the types of bacterial taxa present. Furthermore, C. trachomatis positive women showed an overall decrease in Lactobacillus spp. and an increase in anaerobes. These findings are part of an ongoing larger epidemiological study that will evaluate the potential role of distinct bacterial communities of the cervical microbiota in C. trachomatis infection.
| S-EPMC5509768 | biostudies-literature
Project description:BACKGROUND:Chlamydia trachomatis can cause reproductive morbidities after ascending to the upper genital tract of women, and repeated infection can lead to worse disease. Data related to protective immune responses at the cervical mucosa that could limit chlamydial infection to the cervix and/or prevent reinfection inform vaccine approaches and biomarkers of risk. METHODS:We measured 48 cytokines in cervical secretions from women having chlamydial cervical infection alone (n = 92) or both cervical and endometrial infection (n = 68). Univariable regression identified cytokines associated with differential odds of endometrial infection and reinfection risk, and multivariable stepwise regression identified cytokine ratios associated with differential risk. RESULTS:Elevated interleukin (IL) 15/CXCL10 (odds ratio [OR], 0.55 [95% confidence interval {CI}, .37-.78]), IL-16/tumor necrosis factor-? (OR, 0.66 [95% CI, .45-.93]), and CXCL14/IL-17A (OR, 0.73 [95% CI, .54-.97]) cytokine ratios were significantly (P ? .05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P = .001) associated with a decreased risk of reinfection (hazard ratio, 0.71 [95% CI, .58-.88]). CONCLUSIONS:Cytokines involved in humoral, type I interferon, and T-helper (Th) 17 responses were associated with susceptibility to C. trachomatis, whereas cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.
| S-EPMC6581900 | biostudies-literature
Project description:A sensitive and specific system for detection of amplified Chlamydia trachomatis DNA from cervical specimens by fluorometric quantitation in an enzyme immunoassay (EIA) format (polymerase chain reaction [PCR]-EIA) is described. The primers selected for PCR-amplified DNA were from the 15 serovars of C. trachomatis and two strains of Chlamydia pneumoniae (TWAR). One strain of Chlamydia psittaci (Borg) was not amplified. One hundred four previously cultured cervical specimens were evaluated. Forty-six culture-positive specimens containing from 1+ to 4+ inclusion bodies were all positive by PCR-EIA. Of 58 culture-negative specimens, 2 were repeatedly positive and were nonreactive with control probes. This assay system represents a sensitive and specific combination of technologies for the quantitative detection of C. trachomatis DNA directly from a body fluid.
| S-EPMC268088 | biostudies-other
Project description:BackgroundA role of Chlamydia trachomatis in HPV-induced cervical carcinogenesis has been reported for cervical cancer but studies on cervical adenocarcinoma are limited.MethodsA total of 1,553 cervical smears taken up to 26 years before diagnosis in a large population-based nested case-control study of cervical adenocarcinoma (AC, 132 cases with matched controls), and adenocarcinoma in situ (AIS, 159 cases with matched controls) were tested for C. trachomatis and HPV DNA by a type-specific PCR bead-based multiplex genotyping (TS-MPG) assay.ResultsOnly 1.7% of samples were positive for C. trachomatis, with no significant differences between AC/AIS cases and controls. HPV-positivity was detected in 49.3% of C. trachomatis-negative and 65.4% C. trachomatis-positive samples, respectively.ConclusionsA large prospective study did not find any risk for cervical adenocarcinoma and/or AIS conferred by C. trachomatis infection.ImpactC. trachomatis appears not to be involved in cervical adenocarcinomas.
| S-EPMC4881944 | biostudies-literature
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: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:The aim of this study was to characterize the urine metabolome of women with Chlamydia trachomatis (CT) uro-genital infection (n = 21), comparing it with a group of CT-negative subjects (n = 98). By means of a proton-based nuclear magnetic resonance (1H-NMR) spectroscopy, we detected and quantified the urine metabolites of a cohort of 119 pre-menopausal Caucasian women, attending a STI Outpatients Clinic in Italy. In case of a CT positive result, CT molecular genotyping was performed by omp1 gene semi-nested PCR followed by RFLP analysis. We were able to identify several metabolites whose concentrations were significantly higher in the urine samples of CT-positive subjects, including sucrose, mannitol, pyruvate and lactate. In contrast, higher urinary levels of acetone represented the main feature of CT-negative women. These results were not influenced by the age of patients nor by the CT serovars (D, E, F, G, K) responsible of the urethral infections. Since the presence of sugars can increase the stability of chlamydial proteins, higher levels of sucrose and mannitol in the urethral lumen, related to a higher sugar consumption, could have favoured CT infection acquisition or could have been of aid for the bacterial viability. Peculiar dietary habits of the subjects enrolled, in term of type and amount of food consumed, could probably explain these findings. Lactate and pyruvate could result from CT-induced immunopathology, as a product of the inflammatory microenvironment. Further studies are needed to understand the potential role of these metabolites in the pathogenesis of CT infection, as well as their diagnostic/prognostic use.
| S-EPMC5864028 | biostudies-literature
Project description:The obligate intracellular pathogen Chlamydia trachomatis is the leading cause of noncongenital blindness and causative agent of the most common sexually transmitted infection of bacterial origin. With a reduced genome, C. trachomatis is dependent on its host for survival, in part due to a need for the host cell to compensate for incomplete bacterial metabolic pathways. However, relatively little is known regarding how C. trachomatis is able to hijack host cell metabolism. In this study, we show that two host glycolytic enzymes, aldolase A and pyruvate kinase, as well as lactate dehydrogenase, are enriched at the C. trachomatis inclusion membrane during infection. Inclusion localization was not species specific, since a similar phenotype was observed with C. muridarum Time course experiments showed that the number of positive inclusions increased throughout the developmental cycle. In addition, these host enzymes colocalized to the same inclusion, and their localization did not appear to be dependent on sustained bacterial protein synthesis or on intact host actin, vesicular trafficking, or microtubules. Depletion of the host glycolytic enzyme aldolase A resulted in decreased inclusion size and infectious progeny production, indicating a role for host glycolysis in bacterial growth. Finally, quantitative PCR analysis showed that expression of C. trachomatis glycolytic enzymes inversely correlated with host enzyme localization at the inclusion. We discuss potential mechanisms leading to inclusion localization of host glycolytic enzymes and how it could benefit the bacteria. Altogether, our findings provide further insight into the intricate relationship between host and bacterial metabolism during Chlamydia infection.
| S-EPMC7671904 | biostudies-literature