Effects of sustained antibiotic bactericidal treatment on Chlamydia trachomatis-infected epithelial-like cells (HeLa) and monocyte-like cells (THP-1 and U-937)

Mpiga, Philomène; Ravaoarinoro, M.

doi:10.1016/j.ijantimicag.2005.11.010

Cited by 20 publications

(21 citation statements)

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“…Our study showed that bactericidal Dox treatment also induced persistent C. trachomatis L2 infection [21]. It is important to know whether the transition between active and persistent infection elicited changes in cytokine expression.…”

Section: Discussionmentioning

confidence: 61%

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Sustained Interleukin‐6 and Interleukin‐8 Expression Following Infection with Chlamydia trachomatis Serovar L2 in a HeLa/THP‐1 Cell Co‐culture Model

et al. 2006

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Correspondence to: Dr M. Ravaoarinoro, Département de microbiologie médicale et infectiologie, section de microbiologie clinique, CHUM-Hôtel-Dieu, 3840 rue St-Urbain, Porte 5-206, Montréal, QC H2W 1T8, Canada. E-mail: madeleine.ravaoarinoro.chum@ssss.gouv.qc.ca AbstractChlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-b (IL-1b), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factora (TNF-a)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1b expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-a synthesis was downregulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1b, IL-6, IL-8 and TNF-a expression was reduced, whereas the synthesis of IL-10 and IL12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.

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Section: Discussionmentioning

confidence: 61%

“…It remained in a persistent state, as demonstrated by continuous chlamydial 16s rRNA expression [21]. We may question whether the transition between active and persistent infection came about with altered pro-inflammatory cytokine expression.…”

Section: Effects Of Dox On Cytokine Expressionmentioning

confidence: 99%

Sustained Interleukin‐6 and Interleukin‐8 Expression Following Infection with Chlamydia trachomatis Serovar L2 in a HeLa/THP‐1 Cell Co‐culture Model

et al. 2006

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“…This state is reversible. Several different stimuli have been shown to induce persistence, including (i) gamma interferon treatment, (ii) penicillin treatment, (iii) amino acid (e.g., tryptophan), glucose, and iron deprivation, (iv) chlamydiophage infection, and several others (14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Persistence therefore appears to be a mechanism that allows the organisms to ride out hostile conditions while maintaining a long-term (chronic) infection within a host cell.…”

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confidence: 99%

Evolution to a Chronic Disease Niche Correlates with Increased Sensitivity to Tryptophan Availability for the Obligate Intracellular Bacterium Chlamydia pneumoniae

Huston

Barker

Chacko

2014

Journal of Bacteriology

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bThe chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

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“…Therefore, it is unknown whether any experimental chlamydial vaccine candidates could have a therapeutic effect, whether they might reduce or enhance pathological sequelae, or whether they could cause chronic, persistent infections, when administered during an infection. Knowing that Chlamydia can enter a persistent state when put under various pressures, including cytokine production, [92][93][94][95][96][97][98][99][100][101][102][103][104][105] it is plausible that enhancement of infection-induced immune responses by vaccination may cause the Chlamydia to enter this state and promote both pathology development and future reactivation of infection. It is also unknown whether any vaccine candidates administered after resolution of a previous genital infection will further boost the individual's infection-induced immune response, provide a greater level of protection and prevent further pathology development.…”

Section: Problems With Vaccine Developmentmentioning

confidence: 99%

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

Carey

Beagley

2010

American J Rep Immunol

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Citation Carey AJ, Beagley KW. Chlamydia trachomatis, a hidden epidemic: effects on the female reproduction and options for treatment. Am J Reprod Immunol 2010The number of genital tract Chlamydia trachomatis infections is steadily increasing worldwide, with approximately 50–70% of infections asymptomatic. There is currently no uniform screening practice, current antibiotic treatment has failed to prevent the increased incidence, and there is no vaccine available. We examined studies on the epidemiology of C. trachomatis infections, the effects infections have on the female reproductive tract and subsequent reproductive health and what measures are being taken to reduce these problems. Undetected or multiple infections in women can lead to the development of severe reproductive sequelae, including pelvic inflammatory disease and tubal infertility. There are two possible paradigms of chlamydial pathogenesis, the cellular and immunological paradigms. While many vaccine candidates are being extensively tested in animal models, they are still years from clinical trials. With no vaccine available and antibiotic treatment unable to halt the increased incidence, infection rates will continue to increase and cause a significant burden on health care systems.

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Effects of sustained antibiotic bactericidal treatment on Chlamydia trachomatis-infected epithelial-like cells (HeLa) and monocyte-like cells (THP-1 and U-937)

Cited by 20 publications

References 44 publications

Sustained Interleukin‐6 and Interleukin‐8 Expression Following Infection with Chlamydia trachomatis Serovar L2 in a HeLa/THP‐1 Cell Co‐culture Model

Sustained Interleukin‐6 and Interleukin‐8 Expression Following Infection with Chlamydia trachomatis Serovar L2 in a HeLa/THP‐1 Cell Co‐culture Model

Evolution to a Chronic Disease Niche Correlates with Increased Sensitivity to Tryptophan Availability for the Obligate Intracellular Bacterium Chlamydia pneumoniae

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

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