1,721,081 research outputs found
Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment
No full textThe 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.Full Tex
Chlamydia pneumoniae and Chlamydia Trachomatis Infection Differentially Modulates Human Dendritic Cell Line (MUTZ) Differentiation and Activation
No full textFree to read\ud
\ud
Chlamydia trachomatis and Chlamydia pneumoniae are important human pathogens that infect the urogenital/anorectal and respiratory tracts, respectively. Whilst the ability of these bacteria to infect epithelia is well defined, there is also considerable evidence of infection of leucocytes, including dendritic cells (DCs). Using a human dendritic cell line (MUTZ), we demonstrate that the infection and replication of chlamydiae inside DCs is species and serovar specific and that live infection with C. pneumoniae is required to upregulate costimulatory markers CD80, CD83 and human leucocyte antigen (HLA)-DR on MUTZ cells, as well as induce secretion of interleukin (IL)-2, IL-6, IL-8, IL-12 (p70), interferon-gamma and tumour necrosis factor-alpha Conversely, C. trachomatis serovar D failed to upregulate DC costimulatory markers, but did induce secretion of high concentrations of IL-8. Interestingly, we also observed that infection of MUTZ cells with C. pneumoniae or C. trachomatis serovar L2, whilst not replicative, remained infectious and upregulated lymph node migratory marker CCR7 mRNA. Taken together, these data confirm the findings of other groups using primary DCs and demonstrate the utility of MUTZ cells for further studies of chlamydial infection
Male Genital Tract Chlamydial Infection: Implications for Pathology and Infertility
No full textChlamydia trachomatis infections are prevalent worldwide, but current research, screening and treatment is focussed on females, with the burden of disease and infertility sequelae considered predominantly a female problem. However, the prevalence of chlamydial infection is similar in males and females. Furthermore, a role for this pathogen in the development of male urethritis, epididymitis and orchitis is widely accepted. While the role of Chlamydia in the development of prostatitis is controversial, we suggest that Chlamydia is an aetiological agent, with incidences of up to 39.5% reported in prostatitis patients. Infection of the testis and prostate is implicated in a deterioration of sperm, possibly affecting fertility. Chlamydia infections may also affect male fertility by directly damaging the sperm, as sperm parameters, proportion of DNA fragmentation, and acrosome reaction capacity are impaired with chlamydial infection. Furthermore, the proportion of male partners of infertile couples with evidence of a Chlamydia infection is greater than documented in the general population. An effect of male chlamydial infection on the fertility of the female partner has also been reported. Thus the need for a vaccine to protect both males and females is proposed. The difficulty arises because the male reproductive tract is an immune privileged site which can be disrupted, potentially affecting spermatogenesis, if inappropriate inflammatory responses are provoked. Examination of responses to infection in humans and in experimental animal models suggest that an IgA-inducing vaccine will be able to effectively target the male reproductive tract, while avoiding harmful inflammatory responses that may impair fertility
Oral immunization with a novel lipid-based adjuvant protects against genital Chlamydia infection
No full textOral immunization is attractive as a delivery route because it is needle-free and useful for rapid mass vaccination programs to target pandemics or bioterrorism. This potential has not been realized for human vaccination, due to the requirement of large antigen doses and toxic (to humans) adjuvants to overcome the induction of oral tolerance and potential degradation of antigens in the stomach. To date, only oral vaccines based on live attenuated organisms have been approved for human use. In this study we describe the use of a lipid-based delivery system/adjuvant, Lipid C, for oral immunization to protect mice against genital tract chlamydial infection. Lipid C is formulated from food-grade purified and fractionated triglycerides. Bacterial shedding following vaginal challenge with Chlamydia muridarum was reduced by 50% in female mice orally immunized with the chlamydial major outer membrane protein (MOMP) formulated in Lipid C, protection equivalent to that seen in animals immunized with MOMP admixed with both cholera toxin (CT) and CpG oligodeoxynucleotides (CpG-ODN). Protection was further enhanced when MOMP, CT and CpG were all combined in the Lipid C matrix. Protection correlated with production of gamma interferon (IFN) by splenic T cells, a serum MOMP-specific IgG response and low but detectable levels of MOMP-specific IgA in vaginal lavage
Interleukin 17A is an immune marker for chlamydial disease severity and pathogenesis in the koala (Phascolarctos cinereus)
No full textThe koala (Phascolarctos cinereus) is an iconic Australian marsupial species that is facing many threats to its survival. Chlamydia pecorum infections are a significant contributor to this ongoing decline. A major limiting factor in our ability to manage and control chlamydial disease in koalas is a limited understanding of the koala’s cell-mediated immune response to infections by this bacterial pathogen. To identify immunological markers associated with chlamydial infection and disease in koalas, we used koala-specific Quantitative Real Time PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood Mononuclear Cells (PBMCs) collected from 41 koalas with different stages of chlamydial disease. Target cytokines included the principal Th1 (Interferon gamma; IFNγ), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines (Tumor Necrosis Factor alpha; TNFα). A novel koala-specific IL17A qrtPCR assay was also developed as part of this study to quantitate the gene expression of this Th17 cytokine in koalas. A statistically significant higher IL17A gene expression was observed in animals with current chlamydial disease compared to animals with asymptomatic chlamydial infection. A modest up-regulation of pro-inflammatory cytokines, such as TNFα and IFNγ, was also observed in these animals with signs of current chlamydial disease. IL10 gene expression was not evident in the majority of animals from both groups. Future longitudinal studies are now required to confirm the role played by cytokines in pathology and/or protection against C. pecorum infection in the koala
Vaccination of koalas with a prototype chlamydial vaccine is safe, does not increase the incidence of lymphoma-related disease and maybe associated with increased lifespan in captive koalas
No full textObjectives: To assess the impact of Chlamydia vaccination on survival of captive koalas, and to compare the incidence of lymphomas and neoplasias between vaccinated and unvaccinated koalas. Methods: Survival analysis using Cox and Weibull regressions on 54 vaccinated and 52 matched unvaccinated koalas, and chi-square contingency table for incidence of lymphomas/neoplasias. Results: Vaccination was found to have a significant positive effect on koala lifespan (P = 0.03), with vaccinated koalas having a median lifespan of 12.25 years compared to 8.8 years for unvaccinated ones. The effect of sex on lifespan was not significant (P = 0.31). The risk ratio of unvaccinated over vaccinated koalas was 2.2 with both Cox and Weibull regressions. There was no association between the incidence of lymphoma/neoplasias and vaccination status (P = 0.33). Conclusions: Koalas vaccinated with a prototype Chlamydia vaccine may live longer than unvaccinated ones. There was no known Chlamydia infection among koalas, so our interpretation is that vaccination may have boosted the innate and adaptive immune systems to protect against a wide spectrum of bacteria, fungi and parasites. Vaccinated koalas did not show negative physiological effects of the vaccine, for example, the frequency of deaths due to lymphomas/neoplasias was the same in both vaccinated and unvaccinated animals
The mouse model of Chlamydia genital tract infection: a review\ud of infection, disease, immunity and vaccine development
No full textChlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far
- …
