Trachomatis Infection Research Articles

HLA-DR and HLA-DQ Polymorphism Correlation with Sexually Transmitted Infection Caused by Chlamydia trachomatis.

Background and Objectives: Chlamydia trachomatis (C. trachomatis) represents one of the most prevalent bacterial sexually transmitted diseases. This study aims to explore the relationship between HLA alleles/genotypes/haplotypes and C. trachomatis infection to better understand high-risk individuals and potential complications. Materials and Methods: This prospective study recruited participants from Transylvania, Romania. Patients with positive NAAT tests for C. trachomatis from cervical/urethral secretion or urine were compared with controls regarding HLA-DR and -DQ alleles. DNA extraction for HLA typing was performed using venous blood samples. Results: Our analysis revealed that the presence of the DRB1*13 allele significantly heightened the likelihood of C. trachomatis infection (p = 0.017). Additionally, we observed that individuals carrying the DRB1*01/DRB1*13 and DQB1*03/DQB1*06 genotype had increased odds of C. trachomatis infection. Upon adjustment, the association between the DRB1*01/DRB1*13 genotype and C. trachomatis remained statistically significant. Conclusions: Our findings underscore the importance of specific HLA alleles and genotypes in influencing susceptibility to C. trachomatis infection. These results highlight the intricate relationship between host genetics and disease susceptibility, offering valuable insights for targeted prevention efforts and personalized healthcare strategies.

Association between bacterial vaginosis, Chlamydia trachomatis infection and tubal factor infertility in Bukavu, Democratic Republic of Congo

BackgroundTubal factor infertility (TFI) is common in sub-Saharan Africa and often secondary to pelvic inflammatory disease (PID). Anaerobes associated with bacterial vaginosis (BV) are also found in PIDs widely dominated by Chlamydia trachomatis (C. trachomatis), whose role in TFI is better demonstrated than that of BV.ObjectivesTo determine the prevalence of BV and C. trachomatis and to investigate the association between BV, C. trachomatis and TFI.MethodsWe included 137 patients treated for infertility between January 2020 and November 2021. Cases were defined as women with infertility aged 18-45 years presenting with TFI (n = 52), and controls as infertile women in the same age groups without TFI (n = 85). Data on social habits, life style and infertility parameters were collected, and we performed screening for BV and C. trachomatis. Multiple regression was used to measure associations.ResultsThe prevalence of BV and C. trachomatis was 42.3% (58/137) and 23.4% (32/137), respectively. BV (61.5% vs 30.6%, p<0.001) and C. trachomatis (48.1 vs 8.2%, p<0.001) were more frequent in cases of TFI.BV and C. trachomatis increased the risk of TFI approximately 4-fold [aOR: 3.77 (1.61-8.83), p=0.002] and 14-fold [aOR: 13.77 (4.59-41.27), p<0.001], respectively.ConclusionBV and C. trachomatis infection are strongly associated with TFI in Bukavu. Prevention and screening should be implemented to reduce the risk of TFI.

Efficacy of a novel affitoxin targeting MOMP against Chlamydia trachomatis in vitro and in vivo

Abstract Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas Exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C.trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

Multi-repeat sequences identification using genome mining techniques for developing highly sensitive molecular diagnostic assay for the detection of Chlamydia trachomatis.

Chlamydia trachomatis ( C. trachomatis) is a common sexually transmitted infection (STI). In 2019, the World Health Organization reported about 131 million infections. The majority of infected patients are asymptomatic with cases remaining undetected. It is likely that missed C. trachomatis infections contribute to preventable adverse health outcomes in women and children. Consequently, there is an urgent need of developing efficient diagnostic methods. In this study, genome-mining approaches to identify identical multi-repeat sequences (IMRS) distributed throughout the C. trachomatis genome were used to design a primer pair that would target regions in the genome. Genomic DNA was 10-fold serially diluted (100pg/μL to 1×10 -3pg/μL) and used as DNA template for PCR reactions. The gold standard PCR using 16S rRNA primers was also run as a comparative test, and products were resolved on agarose gel. The novel assay, C. trachomatis IMRS-PCR, had an analytical sensitivity of 4.31 pg/µL, representing better sensitivity compared with 16S rRNA PCR (9.5 fg/µL). Our experimental data demonstrate the successful development of lateral flow and isothermal assays for detecting C. trachomatis DNA with potential use in field settings. There is a potential to implement this concept in miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for reliable point-of-care testing.

T3, T4, TSH, Anti-TPO, and Anti-TG Autoantibodies Distribution in Autoimmune Thyroid Patients with Chlamydia Trachomatis Infection

Autoimmune thyroid disorders (AITDs) include a variety of inflammatory conditions affecting the thyroid gland, with Graves' disease (GD) and Hashimoto's thyroiditis (HT) being the most commonly seen types. Autoimmune thyroid illnesses often include the existence of antibodies against thyroid peroxidase (TPO), thyroglobulin (Tg), and thyroid stimulating hormone receptor (TSHR). We specifically targeted recently diagnosed adult patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and those with normal thyroid function as controls. The study looked at and compared different groups' levels of anti-TG antibodies, anti-TPO antibodies, and anti-chlamydia antibodies in the blood, as well as several clinical and biochemical markers, such as thyroid function tests. We analyzed data from a cohort of 60 patients diagnosed with Hashimoto's thyroiditis (HT), 60 patients diagnosed with Graves' disease (GD), and 60 healthy individuals serving as controls. The study found a strong link between having anti-TPO Abs and having Hashimoto's hypothyroidism (63.3%) and Graves' hyperthyroidism (86.7%). In the groups without anti-TPO Abs, Hashimoto's hypothyroidism was found in 36.7% of people and Graves' hyperthyroidism was found in 13.3% (P&lt;0.03). Anti-thyroid peroxidase antibodies (anti-TPO Abs) are found in 86.7% of people with Graves' disease, which is more than the 63.3% of people with Hashimoto's disease who have these antibodies. There is no significant link between the percentage of people who have anti-TG antibodies and either Hashimoto's hypothyroidism (96.7%) or Graves hyperthyroidism (90%), according to the study. The significance level was set at P = 0.143. This is in comparison to the percentage of negativity in Hashimoto's hypothyroidism (3.3%) and Graves's hyperthyroidism (10.0%). The study showed how the groups were spread out based on the presence of Chlamydia trachomatis IgG antibodies. Chlamydia trachomatis IgG antibodies were much more common in people with Hashimoto's hypothyroidism (42) and Graves hyperthyroidism (26) than in the control group (0) (P&lt;0.01).

Incidence and spontaneous clearance of gonorrhea and chlamydia infections among men who have sex with men: a prospective cohort study in Zhuhai, China.

Men who have sex with men (MSM) face significant risks of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) infection. Nevertheless, only limited studies have looked into the site-specific infection and clearance of CT/NG. In order to prevent transmission, it is essential to understand the underlying factors that drive infection and spontaneous clearance. A 12-week cohort study examined the association between CT/NG infection, self-clearance, and sexual behaviors among MSM. The Willingness Service recruited participants who completed weekly questionnaires and provided urine, throat, and rectal swab samples. The study involved 151 men, in which 51 (33.8%) were diagnosed with CT/NG infection during the study period. HIV (OR = 11.31), kissing (OR = 1.59), receptive oral sex (OR = 36.64), and insertive anal sex (OR = 19.73) constituted significant risk factors. 100% condom use (OR = 5.78) and antibiotic (OR = 7.53) were more likely to cause spontaneous clearance. MSM may engage in riskier sexual behaviors due to insufficient knowledge and awareness of STI prevention, leading to increased susceptibility to NG/CT. It is crucial to concentrate on enhancing health education for MSM. This study found that the rectum was the most prevalent site of CT/NG and sexual behavior can influence the infection. Additionally, the appropriate use of antibiotics and consistent condom use may contribute to clear spontaneously.

Doxycycline adherence for the management of Chlamydia trachomatis infections

BackgroundThe updated 2021 CDC treatment guidelines recommend a single dose of 500 mg intramuscular ceftriaxone for Neisseria gonorrhea and doxycycline 100 mg by mouth twice daily for 7 days for Chlamydia trachomatis coinfection. However, there is a significant public health concern regarding patient non-adherence to the 7-day course of doxycycline. To date, there are no studies assessing this concern. Therefore, the objective of this study was to evaluate a patient's adherence to doxycycline for chlamydial infections after discharge from the Emergency Department (ED). MethodsThis was an IRB-approved, single-center, retrospective cohort study evaluating the adherence to doxycycline for Chlamydia trachomatis infections. Patients who received treatment and were discharged from the ED with a doxycycline e-prescription between May 2021 and September 2022 were included. Patients were excluded if <18 years of age, pregnant, a sexual assault victim, or admitted inpatient. The primary endpoint was the incidence of doxycycline prescription pick-up after discharge from the ED. The secondary endpoint was the incidence of repeat ED visits for the same chief complaint within 28 days. Descriptive statistics were computed for all study variables and Fisher's Exact tests were used to assess the outcomes. ResultsA review of 144 patients who tested positive for chlamydia and were discharged from the ED with an e-prescription for doxycycline revealed that 18% of patients did not pick up their prescription (N = 26). Non-adherent patients were more likely to return to the ED with the same chief complaint within 28 days (23.1% vs 7.6%, OR 3.6 [1.2–11.3], p = 0.026). No differences were detected in baseline demographics, housing status, insurance type, sexual orientation, or Sexually Transmitted Infection history. ConclusionFor patients with a positive chlamydia infection who were discharged from the ED on doxycycline, an 18% non-adherence rate was found and a 3.6-fold higher likelihood of returning to the ED with the same chief complaint if the prescription was not picked up.

Prevalence and host-related factors of Chlamydia trachomatis infection among fertile and infertile people in Ankpa, Kogi State, Nigeria

Prevalence and host-related factors of Chlamydia trachomatis infection among fertile and infertile people in Ankpa, Kogi State, Nigeria

Association of Chlamydia trachomatis Infection With Breast Cancer Risk and the Modification Effect of IL-12

BackgroundChlamydia trachomatis (C. trachomatis) infection has been implicated in various cancers, yet its association with breast cancer remains unexplored. This infection triggers a cascade of immune responses primarily regulated by Interleukins-12 (IL-12). Thus, the objective of this case-control study was to investigate the link between C. trachomatis infection and breast cancer risk, as well as the modification effect of IL-12. MethodsWe assessed IgG levels against C. trachomatis in serum of 1,121 women with breast cancer (861 with estrogen receptor-positive (ER+) and 260 with estrogen receptor-negative (ER-) tumors) and 400 controls in Guangzhou, China. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk in association with C. trachomatis infection. The interaction between C. trachomatis infection and IL-12 on breast cancer risk was estimated by the product terms in the logistic regression models. ResultsSeropositivity of C. trachomatis IgG showed a slight association with an increased risk of breast cancer (OR = 1.20; 95% CI: 0.86∼1.78). This association was more pronounced among women with a higher (OR = 5.82; 95% CI: 1.31∼25.94) than a lower (OR = 0.73; 95% CI: 0.41∼1.30) level of IL-12, with a statistically significant interaction observed (Pinteraction = 0.013). In addition, C. trachomatis IgG seropositivity was related to an increased risk of breast cancer among PR+ patients (OR = 1.53; 95% CI: 1.04∼2.23). ConclusionsC. trachomatis infection may contribute to the development of hormone-responsive breast cancer in women with high levels of IL-12. Further studies are needed to uncover the underlying mechanisms.

Compliance With CDC-Recommended 7-Day Chlamydia Treatment in Nonpregnant Adult Female Patients in Low-Resource Communities: 1-Year Data [ID 2683472

INTRODUCTION: In 2021, the Centers for Disease Control and Prevention (CDC) changed treatment guidelines for chlamydia (Chlamydia trachomatis) infections in nonpregnant women, as substantial data demonstrated oral doxycycline at 100 mg twice daily for 7 days as superior to one-dose oral azithromycin at 1 g. Previously, the two antibiotic regimens were considered equivocal, allowing providers to opt for the shorter regimen course to optimize compliance and cure rate. METHODS: We assessed the compliance rate of patients in low-resource communities to the multidose doxycycline regimen via retrospective chart review. For a 12-month period, all nonpregnant adult female patients prescribed doxycycline for chlamydia infection at a county hospital system were included in the IRB-exempt study. Patients were called 7–10 days after initial doxycycline prescription to assess compliance, medication side effects, and adherence barriers. Noncompliant patients were offered a prescription for the azithromycin regimen. Patients were encouraged to repeat chlamydia testing in 4 weeks to assess for cure, or in 3 months for reinfection. RESULTS: Two hundred sixty-four patients met inclusion criteria, 193 (73.1%) of whom could be contacted. Patients were significantly compliant to multidose doxycycline despite barriers (P=.0002; 95% CI, 3.33–50.48), such as pharmacy-induced medication fill delay and medication side effects. Only 7 (58.3%) noncompliant patients desired to switch to azithromycin. Of the 105 compliant patients re-tested, most (87.6%) tested negative. CONCLUSION: The data demonstrated that patients in low-resource communities are significantly compliant with the CDC-recommended 7-day doxycycline regimen despite barriers to adherence. Therefore, even in low-resource communities, practitioners should prescribe multidose doxycycline for chlamydia infection in nonpregnant females.

Prevalence and associated risk factors of chlamydia and gonorrhoea infections among men who have sex with men in Durban, South Africa.

Despite significant research on the prevalence of STIs in South African men who have sex with men (MSM), recent data on the prevalence and risk factors for curable STI infections among this key populations are limited. This study determined the prevalence of and risk factors associated with Neisseria gonorrhoeae and Chlamydia trachomatis infections among MSM. The sample consisted of 200 MSM resident in Durban. Data were collected using a self-administered questionnaire, and urine samples were collected and tested for N. gonorrhoeae and C. trachomatis. The prevalence of N. gonorrhoeae and C. trachomatis were 3.0% and 6.0%, respectively. Younger age was significantly associated with testing positive for C. trachomatis (p=0.037). Being between the ages of 30-39 years old reduced the risk of acquiring C. trachomatis infection (OR: 0.10, 95% CI: 0.0120-0.7564, p=0.026). In addition, being circumcised reduced the risk of contracting C. trachomatis (adjusted OR: 0.01, 95% CI: 0.0005-0.3516, p=0.01). However, having between 2-4 sex partners increased the risk of testing positive for C. trachomatis (adjusted OR: 107.45, 95% CI: 1.3467-8573.3130, p=0.036). The following factors were significantly associated (p<0.05) with testing positive for N. gonorrhoeae infection: cohabiting with sex partner, engaging in group sex, and drug use. Fear and stigma were the main barriers to accessing health care in the studied population. This study provided evidence of high rates of C. trachomatis infection among MSM resident in Durban. Based on the results, South African MSM, especially the young MSM population, should be given priority when delivering intervention programs to prevent STIs.

Screening of single nucleotide polymorphism in matrix metalloproteinase-2 (MMP2) and tetraspanin CD63 genes in Chlamydia trachomatis-infected tubal ectopic pregnancy patients.

Tubal ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality. Studies have suggested that infection-induced inflammatory responses are major risk factors for EP. The aim of the present study was to find an association between MMP2 and CD63 gene variants and risk of EP during Chlamydia trachomatis infection in an Indian population. Fallopian tube samples of 120 EP and 120 tubal ligation women were collected. C. trachomatis was detected by PCR. The genotyping of MMP2 (rs17859882 G/T, rs7201A/C) and CD63(rs2231464 C/T, rs376086542 A/G) gene variants was done by qualitative real-time PCR using allelic discrimination method (VIC- and FAM-labeled). The frequency of GG or GT genotype of MMP2 G/T polymorphism (rs17859882) was 66.6% in infected EP and 36.7% in uninfected EP and 22% in tubal ligation controls (P < 0.0001), while the frequency of AC or CC genotype of MMP2 A/C polymorphism (rs7201) was 66.6% in infected EP and 20.6% in uninfected EP and 13.5% in tubal ligation controls (P < 0.0001). The frequency of CT or TT genotype of CD63 C/T polymorphism (rs2231464) was 74% in infected EP and 21.8% in uninfected EP and 11.8% tubal ligation controls (P < 0.0001), while the frequency of AG or GG genotype of CD63 A/G polymorphism (rs376086542) was 48.1% in infected EP and 41.3% in uninfected EP and 18.6% tubal ligation controls (P < 0.0001). The present study revealed a strong association between the presence of gene variants MMP2 (rs17859882 G/T, rs7201A/C) and CD63 (rs2231464 C/T, rs376086542 A/G) and risk of tubal EP during C. trachomatis infection.

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs.

Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options-twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Characterization of genital chlamydia trachomatis infection among women attending infertility and gynecology clinics in Hunan, China

BackgroundGenital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics.MethodsEndocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays.ResultsHigh C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219–39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284–7.315, p < 0.001).ConclusionOur results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.

Testing the Adaptive Sterilization Hypothesis in mice inoculated with Chlamydia muridarum.

The "adaptive sterilization hypothesis" argues that the tendency of sexually transmitted infections (STIs) to cause infertility likely reflects an evolutionary adaptation of these pathogens. For example, some STIs can lead to bilateral occlusions of the oviducts and sterile matings. Cycling females that do not spend time gestating and lactating are ready to mate sooner than fertile females, and therefore, likely to mate more frequently and possibly more promiscuously. These sexual activities are associated with enhanced transmissibility of STIs, and tubal occlusion is a proximate mechanism by which STIs can increase fitness. Our principal objectives were to determine whether female mice inoculated with Chlamydia muridarum mate more frequently than mice inoculated with sterile saline and to test the hypothesis that tubal occlusion following C. muridarum infection modulates mating behavior in a manner that might increase transmissibility of Chlamydia. Similar to C. trachomatis infections in human females, C. muridarum can ascend the reproductive tract of mice, damage and occlude the oviducts, and cause infertility. However, ovarian function and mating activity are maintained following tubal occlusion. Twenty C57Bl/6 mice with regular estrous cycles were given intra-vaginal inocula of C. muridarum and 32 days later paired with a male for 90 days. Nine saline-treated females served as controls. Three Chlamydia-inoculated females were rendered infertile due to bilateral oviductal damage and mated 8 (±0.0) times. Control females mated on average 4.6 (±0.3) times, and 17 Chlamydia-inoculated fertile females, including six females with only a single oviduct occluded, mated on average 4.7 (±0.2) times. Chlamydia-inoculated fertile females with unilateral oviductal damage had significantly smaller average litter sizes as compared to females inoculated with saline. Females with unilateral tubal occlusion also tended to wean fewer pups than saline controls over the course of 90 days. Female mice with Chlamydia-induced tubal infertility mated more frequently (approximately every 11 d) than did fertile females (approximately every 20 d), which is consistent with the adaptive sterilization hypothesis. To determine whether Chlamydia-induced sterilization is truly adaptive, future studies will need to demonstrate increased sexual transmissibility, and possibly increased promiscuity, within populations of freely breeding mice.

Chlamydia trachomatis and Neisseria gonorrhoeae rectal infections: Interplay between rectal microbiome, HPV infection and Torquetenovirus.

Men having sex with men (MSM) represent a key population, in which sexually transmitted rectal infections (STIs) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and high-risk HPV (HR-HPV) are very common and linked to significant morbidity. Investigating the anorectal microbiome associated with rectal STIs holds potential for deeper insights into the pathogenesis of these infections and the development of innovative control strategies. In this study, we explored the interplay at the rectal site between C. trachomatis, N. gonorrhoeae, HR-HPV infection, and the anorectal microbiome in a cohort of 92 MSM (47 infected by CT and/or NG vs 45 controls). Moreover, we assessed the presence of Torquetenovirus (TTV), a non-pathogenic endogenous virus, considered as a possible predictor of immune system activation. We found a high prevalence of HR-HPV rectal infections (61%), especially in subjects with a concurrent CT/NG rectal infection (70.2%) and in people living with HIV (84%). In addition, we observed that TTV was more prevalent in subjects with CT/NG rectal infections than in non-infected ones (70.2% vs 46.7%, respectively). The anorectal microbiome of patients infected by CT and/or NG exhibited a reduction in Escherichia, while the presence of TTV was significantly associated with higher levels of Bacteroides. We observed a positive correlation of HR-HPV types with Escherichia and Corynebacterium, and a negative correlation with the Firmicutes phylum, and with Prevotella, Oscillospira, Sutterella. Our findings shed light on some of the dynamics occurring within the rectal environment involving chlamydial/gonococcal infections, HPV, TTV, and the anorectal microbiome. These data could open new perspectives for the control and prevention of STIs in MSM.

Chlamydia muridarum Associated Pulmonary and Urogenital Disease and Pathology in a Colony of Enzootically Infected Il12rb2 Deficient and Stat1 Knockout Mice.

Chlamydia muridarum (Cm), an intracellular bacterium of historical importance, was recently rediscovered as moderately prevalent in research mouse colonies. Cm was first reported as a causative agent of severe pneumonia in mice about 80 y ago, and while it has been used experimentally to model Chlamydia trachomatis infection of humans, there have been no further reports of clinical disease associated with natural infection. We observed clinical disease and pathology in 2 genetically engi- neered mouse (GEM) strains, Il12rb2 KO and STAT1 KO, with impaired interferon-γ signaling and Th1 CD4+ T cell responses in a colony of various GEM strains known to be colonized with and shedding Cm. Clinical signs included poor condition, hunched posture, and poor fecundity. Histopathology revealed disseminated Cm with lesions in pulmonary, gastrointestinal, and urogenital tissues. The presence of Cm was confirmed using both immunohistochemistry for Cm major outer membrane protein-1 antigen and in situ hybridization using a target probe directed against select regions of Cm strain Nigg. Cm was also found in association with a urothelial papilloma in one mouse. These cases provide additional support for excluding Cm from research mouse colonies.

DEFB126 2-nt Deletion (rs11467417) as a Potential Risk Factor for Chlamydia Trachomatis Infection and Subsequent Infertility in Iranian Men.

Chlamydia trachomatis (CT) is one of the most prevalent sexually transmitted infections, causing genital tract infections and infertility. Defensins have an immunomodulatory function and play an important role in sperm maturation, motility, and fertilization. DEFB126 is present on ejaculated spermatozoa and is essential for them to pass through the female reproductive tract. The purpose of the study was to determine the frequency of the 2-nt deletion of the DEFB126 (rs11467417) in Iranian infertile males with a recurrent history of CT. Semen samples of 1080 subfertile males were investigated. Among patients who had CT-positive results, sperm DNA from 50 symptomatic and 50 asymptomatic patients were collected for the DEFB126 genotype analysis. Additionally, a control group comprising 100 DNA samples from individuals with normal spermogram and testing negative for CT was included in the study. The PCR-sequencing for detecting the 2-nt deletion of the second exon of the DEFB126 was performed. The Chi-squared test comparing all three groups revealed no significant difference across the different genotypes. Moreover, no significant difference between the symptomatic and asymptomatic groups was seen. However, analysis within CT-positive patients and controls demonstrated significant difference between the frequencies of homozygous del/del. The higher frequency of the 2-nt deletion of the DEFB126 in CT- positive patients suggests that the occurrence of mutations in the DEFB-126 may cause the impairment of the antimicrobial activity of the DEFB126 protein and consequently makes individuals more susceptible to infections such as CT.

IFNγ insufficiency during mouse intra-vaginal Chlamydia trachomatis infection exacerbates alternative activation in macrophages with compromised CD40 functions

Chlamydia trachomatis (C.tr), an obligate intracellular pathogen, causes asymptomatic genital infections in women and is a leading cause of preventable blindness. We have developed in vivo mouse models of acute and chronic C. trachomatis genital infection to explore the significance of macrophage-directed response in mediating immune activation/suppression. Our findings reveal that during chronic and repeated C. trachomatis infections, Th1 response is abated while Treg response is enhanced. Additionally, an increase in exhaustion (PD1, CTLA4) and anergic (Klrg3, Tim3) T cell markers is observed during chronic infection. We have also observed that M2 macrophages with low CD40 expression promote Th2 and Treg differentiation leading to sustained C. trachomatis genital infection. Macrophages infected with C. trachomatis or treated with supernatant of infected epithelial cells drive them to an M2 phenotype. C. trachomatis infection prevents the increase in CD40 expression as observed in western blots and flow cytometric analysis. Insufficient IFNγ, as observed during chronic infection, leads to incomplete clearance of bacteria and poor immune activation. C. trachomatis decapacitates IFNγ responsiveness in macrophages via hampering IFNγRI and IFNγRII expression which can be correlated with poor expression of MHC-II, CD40, iNOS and NO release even following IFNγ supplementation. M2 macrophages during C. trachomatis infection express low CD40 rendering immunosuppressive, Th2 and Treg differentiation which could not be reverted even by IFNγ supplementation. The alternative macrophages also harbour high bacterial load and are poor responders to IFNγ, thus promoting immunosuppression. In summary, C. trachomatis modulates the innate immune cells, attenuating the anti-chlamydial functions of T cells in a manner that involves decreased CD40 expression on macrophages.

Antibodies from chlamydia-infected individuals facilitate phagocytosis via Fc receptors.

Non-neutralizing functions of antibodies, including phagocytosis, may play a role in Chlamydia trachomatis (CT) infection, but these functions have not been studied and assays are lacking. We utilized a flow-cytometry-based assay to determine whether serum samples from a well-characterized cohort of CT-infected and naïve control individuals enhanced phagocytosis via Fc-receptor-expressing THP-1 cells, and whether this activity correlated with antibody titers. Fc-receptor-mediated phagocytosis was detected only in CT+ donors. Phagocytosis generally did not correlate well with antibody titer. In addition, we found that complement from both CT+ and negative individuals enhanced phagocytosis of CT into primary neutrophils. These results suggest that anti-CT antibodies can have functions that are not reflected by titer. This method could be used to quantitively measure Fc-receptor-mediated function of anti-CT antibodies or complement activity and could reveal new immune correlates of protection.