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Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we showed in C. trachomatis-positive women that the NLRP3 mutant AG and AA genotypes were a risk factor for the development of symptoms (P = 0.047, OR = 2.9) and more specifically for having lower abdominal pain (genotype AA: P = 0.022, OR = 31.3). In the Finnish tubal pathology group versus the control group no statistical significant differences in the incidences of the SNPs studied were found, nor for the degree of tubal pathology. In conclusion, the mutant NLRP3 A allele is a risk factor for the development of symptoms, specifically lower abdominal pain, after a C. trachomatis infection in women attending an STD clinic., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium in the world with almost 100 million new cases each year, some of which will develop tubal pathology. Clear differences in its clinical course of infections have been observed, and recently it has been shown that 40% is based on host genetic factors. We used an integrated approach based on infection of Toll-like receptor 4 (TLR4) knockout mice and immunogenetic analysis of female sexually transmitted disease (STD) patients (susceptibility) and women with C. trachomatis-associated tubal factor subfertility (severity). The results in TLR4 knockout mice suggest that the protection against reinfection is more solid in normal as compared to the TLR4-deficient mice. In humans the functional TLR4 single nucleotide polymorphism studied was not involved in the susceptibility to infection. However, C. trachomatis immunoglobulin (Ig) G-positive subfertile women with tubal pathology were more than twice as likely to be carriers of the mutant TLR4 +896 G allele as compared to those without tubal pathology; however this observation did not reach statistical significance. In conclusion, both the murine model and the human immunogenetics studies show a slight effect upon TLR4 deficiency in the severity of infection but not in the susceptibility to infection., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

The data on serovar distributions of Chlamydia trachomatis - the most diagnosed sexually transmitted infection (STI) worldwide - are important for epidemiologic purposes and transmission studies but are completely lacking in Russia. The aim of the current study is to determine the serogroup and serovar distributions in Russian men and women and compare these data with Dutch serogroup and serovar distributions. In Russian men and women, serogroup B was the most prevalent (46%), followed by the intermediate serogroup (I group; 33%) and serogroup C (21%). The distribution was comparable between men and women. The serogroup distribution was similar to the previously published distribution in Dutch cohorts. However, on a serovar level statistically very significant differences were observed, reaching up to P < 0.0001. The serovars B and G/Ga had higher prevalences compared with the reported Dutch prevalences, while serovars F, H, I/Ia, J and K had lower prevalences compared with the Dutch studies. In conclusion, this is the first report of Russian C. trachomatis serovar/serogroup distributions. Serogroup B is the most prevalent, followed by serogroup I and serogroup C with no statistical differences on the serogroup level. However, significant differences between Russia and the Netherlands were observed in the distribution of C. trachomatis serovars., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Chlamydia trachomatis infections are responsible for the world's leading cause of blindness (trachoma) and its most prevalent sexually transmitted disease, which is strongly associated with pelvic inflammatory disease, ectopic pregnancy and tubal infertility. Twin study-based findings of members of EpiGenChlamydia Consortium estimate that there is a 40% genetic predisposition to C. trachomatis infections. It is likely that the advances in human genomics will help to unravel the genetic predisposition at the gene level and will help to define a genetic fingerprint that can be used as a marker for this predisposition. The information gathered to date suggests that this predisposition and the factors contributing to prognosis are multifactorial. The EpiGenChlamydia Consortium aims to structure transnational research to such a degree that comparative genomics and genetic epidemiology can be performed in large numbers of unrelated individuals. Biobanking and data-warehouse building are the most central deliverables of the Coordination Action of the Consortium in Functional Genomics Research. In addition, the collective synergy acquired in this Coordination Action will allow for the generation of scientific knowledge on the C. trachomatis-host interaction, knowledge on the genetic predisposition to C. trachomatis infection and the development of tools for early detection of a predisposition to C. trachomatis infection and its complications. This review summarizes the consortium aims and progress, and future perspectives and directions., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Previous studies have investigated the role of Toll-like receptor (TLR)2 and TLR4 in susceptibility to and severity of Chlamydia trachomatis infections. In this study we employ a unique integrated approach to study the role of the intracellular CpG DNA receptor: we use a murine knockout (KO) model to assess TLR9 relevance, study human TLR9 genotypes and haplotypes in sexually transmitted disease (STD) patients and subfertile women with or without tubal pathology and use in silico TLR9 CpG index calculations to assess potential immunostimulatory properties of the Chlamydia bacterium. Although no significant differences in the course of initial infections were observed between KO mice and wild-type mice the TLR9 KO mice showed a significant level of protection upon reinfection (P = 0.02). We did not observe significant differences in genotype frequencies between C. trachomatis-positive and C. trachomatisnegative women (STD patients). However, haplotype analyses revealed a trend between C. trachomatis-positive and C. trachomatis-negative women in the carriage of haplotype IV (P = 0.061; OR: 2.6; 95% CI: 1.0-6.8). In women with subfertility, odds ratios between 2 and 3 were found for tubal pathology risk, but they did not reach significance due to cohort size limitations. Finally, CpG sequence analysis showed mildly immunostimulatory properties for the genomic sequences of Chlamydia serovars B and D. Based on the murine model, human immunogenetic studies and in silico CpG index analyses, TLR9 seems to play a modest role in C. trachomatis infections. Extension of the human cohorts is necessary to significantly prove the effect in humans., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Chlamydia trachomatis infections may cause several disease conditions ranging from asymptomatic infections to severe upper genital tract pathology, thereby causing significant morbidity worldwide. Remarkable interindividual differences in the clinical course of C. trachomatis infection have been observed, and are mainly based on variation in genes encoding immune-regulatory and bacteria-sensing proteins. Toll-like receptors (TLRs) are closely involved in pathogen recognition and host defense in C. trachomatis infections. The aim of this study is to assess the role of TLR2 single nucleotide polymorphisms and haplotypes in the susceptibility to, and severity of C. trachomatis infections. The study comprised a sexually transmitted disease cohort of 468 Dutch Caucasian women and a control group of 321 women. The subfertility cohort consisted of 56 women with clinically well-defined tubal pathology. The results showed no significant differences in individual TLR2 genotype frequencies in the susceptibility for C. trachomatis infections between the C. trachomatis-positive group and controls. However, haplotype 1 was statistically significant (P = 0.015) and was associated with protection against tubal pathology following C. trachomatis infection. The same haplotype was also significantly decreased (P = 0.021) in increasing severity of C. trachomatis infections (asymptomatic > symptomatic > tubal pathology) suggesting a protective effect of this haplotype against the development of late complications., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

The desire for an integrated approach to the study of Chlamydia trachomatis infection of the female genital tract resulted in the creation of the "ICTI Consortium" (Integrated approach to the study of Chlamydia Trachomatis Infection) in 2005. The ICTI consortium is based on tight interaction and collaboration between basic scientists, clinicians, epidemiologists and health-care policy makers. This translational approach will help to further the valuable insight into the immunopathogenesis of this sexually transmitted infection in order to develop new intervention strategies, including the vaccines and screening programs necessary to effectively diagnose, treat and prevent C. trachomatis infection. This article provides an update of ICTI Consortium activities carried out until September 2009., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Chlamydia trachomatis serovars are divided into three serogroups, namely serogroup B, serogroup I (Intermediate) and serogroup C, and subsequently into 19 different serovars. Worldwide, serogroup B is the most prevalent followed by serogroup I. Clear differences have been observed in the duration of infection and growth kinetics between serovars from different serogroups in murine and cell culture models. Reasons for these observed differences are bacterial and host related, and are not well understood. The aim of this study was to determine the differences in immunoglobulin (Ig) G responses between the three serogroups in a group of patients infected with different serovars. Serovars were assessed from 235 C. trachomatispositive patients and quantitative IgG responses were determined. Analyses of variance were used to compare the IgG responses between the three serogroups. Of the serovars, 46% were B group (with serovar E the most prevalent: 35.3%), 39.6% were I group and 14.3% were C group. A highly significant difference in serologic response was shown when comparing the mean IgG concentrations (AU/mL) of patients having serovars in the most prevalent serogroup compared to the other serogroups: B = 135, C = 46 and I = 60 (B vs. C and B vs. I, P < 0.001). In conclusion, the most prevalent serovars generate the highest serologic responses., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

The combination of bioinformatics, genomics and proteomics is a rapidly expanding research field that has now become essential for the investigation of biological, cellular and molecular phenomena, both in terms of established facts and in prediction models based on simulations, and therefore can greatly contribute to the development of potential new therapeutic approaches. This article provides numerous, well-known examples illustrating the importance of bioinformatics in modern biological and medical research in the field of infectious diseases, specifically Chlamydia trachomatis infection. Specialized chlamydia databases and analysis programs and the information they contain provide the opportunity for understanding and identifying key processes and phenomena associated with the unique infection cycle of chlamydia, and are paving the way towards the development of novel diagnostic and therapeutic tools. Bioinformatics may provide the clues necessary for a true breakthrough in the fight against chlamydial diseases: the development of a vaccine., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)