Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective

Pietro, Marisa Di; Filardo, Simone; Romano, Silvio; Sessa, Rosa

doi:10.3390/microorganisms7050140

Cited by 34 publications

(35 citation statements)

References 150 publications

(211 reference statements)

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“…It is estimated, indeed, that approximately 4-8% of patients will develop ReA one to six weeks after a urogenital C. trachomatis infection [5]. In 30% of all cases, ReA persists for years, compromising joint function and leading, eventually, to joint deformities and ankylosis [6,7]. The involvement of C. trachomatis in ReA has been supported by studies showing chlamydial DNA, RNA, and proteins in synovial fluid, as well as by in vitro studies, demonstrating the ability of C. trachomatis to infect synovial fibroblasts [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts

Pietro¹,

Filardo²,

Frasca

et al. 2020

Microorganisms

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Chlamydia trachomatis, an obligate intracellular pathogen, is the most common cause of bacterial sexually transmitted diseases, and it is potentially responsible for severe chronic sequelae, such as reactive arthritis. To date, details of the mechanisms by which Chlamydiae induce innate antimicrobial pathways in synovial fibroblasts, are not well characterized; therefore, herein, we investigated the effects of interferon (IFN)α, IFNβ, and IFNγ on the infection, and replication phases of the C. trachomatis developmental cycle, as well as on the induction of pattern recognition receptors (PRRs) and IFN-related pathways. To do so, we set up an in vitro chlamydial-infection model of primary human synovial cells treated with IFNs before or after the infection. We then determined the number of chlamydial inclusion forming units and inclusion size, as well as the expression of toll like receptor (TLR)2, TLR3, TLR4, cyclic GMP-AMP synthase (cGAS), stimulator of IFN gene (STING), IRF9, ISG56, and GBP1. The main result of our study is the significant inhibition of C. trachomatis infection and replication in human synovial cells following the treatment with IFNγ, whereas IFN-I proved to be ineffective. Furthermore, IFNγ greatly upregulated all the PRRs and ISGs examined. In conclusion, IFNγ exhibited a potent anti-Chlamydia activity in human synovial cells as well as the ability to induce a strong increase of innate immune pathways.

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Section: Introductionmentioning

confidence: 99%

Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts

Pietro¹,

Filardo²,

Frasca

et al. 2020

Microorganisms

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“…Results showed the highest absorbance values at 36 hours (3.76x10 6 ± 2.24x10 5 A.U.) as compared to values found at 2 hours (2.1x10 4 ± 4.03x10 3 ), 24 hours (3.06x10 6 ± 9.8x10 4 A.U.) and 48 hours (3.08x10 6 ± 7.95x10 4 A.U.…”

Section: Set-up and Optimization Of The Icw Assaymentioning

confidence: 80%

“…Chlamydia trachomatis is the leading infectious cause of blindness among world's poorest people, and, in developed countries, it is one of the major bacterial sexually transmitted pathogens with approximately 127 million new infections per year [1,2]. In women, C. trachomatis manifests as cervicitis and salpingitis while, in men, it is mainly responsible for urethritis [3][4][5]. Furthermore, it can be transmitted to infants following the direct contact with infective cervical secretions during delivery, resulting in neonatal conjunctivitis and pneumonitis [5].…”

Section: Introductionmentioning

confidence: 99%

In-cell western assay as a high-throughput approach for Chlamydia trachomatis quantification and susceptibility testing to antimicrobials

Filardo¹,

Pietro²,

Pasqualetti³

et al. 2021

PLoS ONE

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Chlamydia trachomatis, the leading cause of bacterial sexually transmitted diseases in developed countries, with around 127 million new cases per year, is mainly responsible for urethritis and cervicitis in women, and urethritis and epididymitis in men. Most C. trachomatis infections remain asymptomatic (>50%) and, hence, untreated, leading to severe reproductive complications in both women and men, like infertility. Therefore, the detection of C. trachomatis as well as the antimicrobial susceptibility testing becomes a priority, and, along the years, several methods have been recommended, like cell culture and direct immunofluorescence (DFA) on cell cultures. Herein, we described the application of In-Cell Western assay (ICW) via Odyssey CLx as a fast, more accessible, and high-throughput platform for the quantification of C. trachomatis and the screening of anti-chlamydial drugs. As a first step, we set up a standard curve by infecting cell monolayers with 2-fold serial dilutions of C. trachomatis Elementary Body (EB) suspension. Then, different unknown C. trachomatis EB suspensions were quantified and the chlamydial susceptibility testing to erythromycin was performed, using the DFA as comparison. Our results showed a very high concordance between these two assays, as evidenced by the enumeration of chlamydial IFUs as well as the determination of erythromycin Minimum Inhibitory Concentration (MIC). In conclusion, the ICW assay may be a promising candidate as an accurate and accessible methodology for C. trachomatis antimicrobial susceptibility testing.

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“…6). The upregulation of these pathways in host cells infected with the persistent forms of C. trachomatis may serve as immune surveillance or manipulation of the host immune system to allow the pathogen to escape [31].…”

Section: Discussionmentioning

confidence: 99%

Host cell response and distinct gene expression profiles at different stages of Chlamydia trachomatis infection reveals stage-specific biomarkers of infection

et al. 2021

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Background Chlamydia trachomatis is the most common sexually transmitted infection and the bacterial agent of trachoma globally. C. trachomatis undergoes a biphasic developmental cycle involving an infectious elementary body and a replicative reticulate body. Little is currently known about the gene expression dynamics of host cell mRNAs, lncRNAs, and miRNAs at different stages of C. trachomatis development. Results Here, we performed RNA-seq and miR-seq on HeLa cells infected with C. trachomatis serovar E at 20 h post-infection (hpi) and 44 hpi with or without IFN-γ treatment. Our study identified and validated differentially expressed host cell mRNAs, lncRNAs, and miRNAs during infection. Host cells at 20 hpi showed the most differential upregulation of both coding and non-coding genes while at 44 hpi in the presence of IFN-γ resulted in a dramatic downregulation of a large proportion of host genes. Using RT-qPCR, we validated the top 5 upregulated mRNAs and miRNAs, which are specific for different stages of C. trachomatis development. One of the commonly expressed miRNAs at all three stages of C. trachomatis development, miR-193b-5p, showed significant expression in clinical serum samples of C. trachomatis-infected patients as compared to sera from healthy controls and HIV-1-infected patients. Furthermore, we observed significant upregulation of antigen processing and presentation, and T helper cell differentiation pathways at 20 hpi whereas T cell receptor, mTOR, and Rap1 pathways were modulated at 44 hpi. Treatment with IFN-γ at 44 hpi showed the upregulation of cytokine-cytokine receptor interaction, FoxO signaling, and Ras signaling pathways. Conclusions Our study documented transcriptional manipulation of the host cell genomes and the upregulation of stage-specific signaling pathways necessary for the survival of the pathogen and could serve as potential biomarkers in the diagnosis and management of the disease.

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Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective

Cited by 34 publications

References 150 publications

Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts

Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts

In-cell western assay as a high-throughput approach for Chlamydia trachomatis quantification and susceptibility testing to antimicrobials

Host cell response and distinct gene expression profiles at different stages of Chlamydia trachomatis infection reveals stage-specific biomarkers of infection

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