Search Results (77)

Chlamydia trachomatis has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they may result in severe reproductive sequelae including infertility. A better understanding of C. trachomatis cell biology and bacterial–host cell interactions may be helpful to identify strategies able to counter its transmission among the population, as well as its dissemination in reproductive tissues, reducing the risk of developing severe reproductive sequelae. Therefore, the present review aims to summarize the evidence on the interplay between C. trachomatis and the host defence factors within the cervicovaginal environment. The sophisticated strategies employed by this clinically significant pathogen to counteract these mechanisms are also discussed. In the literature, the main defence factors include the microbiota dominated by Lactobacillus crispatus and several molecules like lactoferrin, able to protect the cervicovaginal microenvironment against C. trachomatis through several mechanisms (e.g., EB coaggregation and competitive exclusion, as well as anti-inflammatory activity). However, the major player in clearing chlamydial infections remains the interferon-gamma (IFN-γ) produced by natural killer and T cells, via the depletion of critical nutrients for C. trachomatis such as tryptophan, or via the ubiquitylation and destruction of chlamydial inclusions. Full article

The relationship between asthma, infections, and immunodeficiencies is complex and affects disease progression. Immune deficiencies can occur independently or because of the inflammatory processes associated with asthma. Early viral infections like respiratory sinticial virus and rhinovirus trigger asthma attacks, while bacteria such as Haemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia pneumoniae worsen airway inflammation. People with asthma often have defects in innate (mucociliary clearance, interferons, defensins, NK cell, and eosinophils) and adaptive immunity such as immunoglobulin (Ig) deficiencies, making them more vulnerable to lung infections. Combined and selective deficiencies of IgA, IgG, IgM, and IgE are linked to higher asthma rates and reduced effectiveness of treatments, but immunoglobulin therapy can help control symptoms. Biologic therapies also decrease asthma exacerbations during periods of high viral activity by boosting immune responses and airway defenses. However, the link between asthma and higher infection risk is not well studied or understood, so guidelines do not recommend routinely checking for immunodeficiencies in cases of poor treatment response. Further investigation is required to elucidate these relationships and enhance management approaches. Full article

Neutrophils are among the first cells to be recruited to the lungs during Chlamydia pneumoniae infection in mouse models; however, their regulatory functions are not yet fully understood. This study examined the mechanisms and significance of IL-10-producing neutrophils throughout C. pneumoniae pulmonary infection in C57BL/6 mice. Our findings revealed that infection with C. pneumoniae induces IL-10 secretion in bone marrow-derived neutrophils, depending on Toll-like receptor 2 (TLR2) activation. This process involves TLR2-dependent mitochondrial reactive oxygen species (ROS) production, which triggers the endoplasmic reticulum (ER) stress pathway, including IRE1α and subsequent Xbp1 splicing. Inhibition of this pathway or depletion of neutrophils (using the 1A8 monoclonal antibody) significantly reduces IL-10 levels in bronchoalveolar lavage fluid (BALF) in vivo. Conversely, the absence of IL-10-producing neutrophils, whether through depletion or TLR2 deficiency, leads to increased IL-12p70 and IFN-γ-positive NK cells, along with decreased regulatory T cells and M2-like macrophages. This results in a lower bacterial burden in the lungs but causes more severe pulmonary damage and decreased survival rates. These findings highlight that IL-10 produced by neutrophils via the TLR2-mitochondrial ROS–ER stress pathway is essential for modulating pulmonary immune responses and maintaining immune homeostasis during C. pneumoniae infection, thereby preventing excessive inflammation and tissue damage. Full article

Aquaculture plays a vital role in meeting the global demand for high-quality protein. However, the fish industry is challenged by infectious diseases, including gill conditions such as epitheliocystis. Epitheliocystis is characterized by cyst-like epithelial lesions, which occur in the gills of fish, and is associated with intracellular bacteria including Chlamydia-related bacteria. Although epitheliocystis was initially regarded as of low significance, attention is increasing due to its impact on commercially important fish species in intense farming conditions. This review evaluates the roles of aquatic chlamydiae as pathogens contributing to fish morbidity and mortality, and as members of fish microbiota. Additionally, Chlamydia-related bacteria are thought to be involved in complex gill disease (CGD), characterized by lamellar fusion, epithelial hyperplasia, and inflammation. Recent discoveries have expanded the diversity of Chlamydiota isolated from fish, with novel species such as Candidatus (Ca.) Panilichlamydia rohitae, Ca. Piscichlamydia trichopodus, and Chlamydia vaughanii identified in different fish hosts. Most causative agents of epitheliocystis have not yet been cultured in vitro, although C. vaughanii, the first Chlamydiaceae member isolated from fish, was successfully cultured. As C. vaughanii was recently shown to be able to propagate in mammalian cells, it raises concerns about its zoonotic potential, although a pathogenic role has yet to be described. Full article

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration. Full article

Background: Heparan sulfate (HS) is widely implicated as a receptor for Chlamydia cell attachment and infectivity. However, the enzymatic modification of HS modified by the 3-O sulfotransferase-3 (3-OST-3) enzyme in chlamydial cell entry remains unknown. Methodology: To rule out the possibility that host cell 3-O sulfated heparan sulfate (3-OS HS) plays a significant role in C. muridarum entry, a Chinese hamster ovary (CHO-K1) cell model lacking endogenous 3-OST-3 was used. In addition, we further tested the efficacy of the phage-display-derived cationic peptides recognizing heparan sulfate (G1 peptide) and the moieties of 3-O sulfated heparan sulfate (G2 peptide) against C. muridarum entry using human cervical adenocarcinoma (HeLa 229) and human vaginal epithelial (VK2/E6E7) cell lines. Furthermore, molecular dynamics simulations were conducted to investigate the interactions of the Chlamydia lipid bilayer membrane with the G1 and G2 peptides, focusing on their binding modes and affinities. Results: The converse effect of 3-OST-3 expression in the CHO-K1 cells had no enhancing effect on C. muridarum entry. The G2 peptide significantly (>80%) affected the cell infectivity of the elementary bodies (EBs) at all the tested concentrations, as evident from the reduced fluorescent staining in the number of inclusion bodies. The observed neutralization effect of G2 peptide on C. muridarum entry suggests the possibility of sulfated-like domains being present on the EBs. In addition, data generated from our in silico computational structural modeling indicated that the G2 peptide ligand had significant affinity towards the C. muridarum lipid bilayer. Conclusions: Taken together, our findings show that the pretreatment of C. muridarum with 3-O sulfated heparan sulfate recognizing G2 peptide significantly prevents the entry of EBs into host cells. Full article

Introduction: Vaginal microbiota has emerged as an important factor influencing human papillomavirus (HPV) persistence and host immunity. While HPV infection is often transient, persistent infections with high-risk HPV genotypes significantly increase the risk of cervical carcinogenesis. Thus, this study aims to investigate the association between microflora/sexually transmitted infections (STIs) and HPV infection, with a focus on the prevalence of coinfection and the potential role of genital tract microecological disorders. Methods: A prospective cohort study was conducted at a tertiary care center in Astana, Kazakhstan, between November 2024 and March 2025. A total of 396 non-pregnant women aged 18–45 years were enrolled during routine gynecological screening. Cervical samples were collected for high-risk HPV genotyping and the detection of 11 other vaginal microorganisms using real-time PCR. Results: HPV-positive women were significantly younger and more likely to be single compared to HPV-negative participants. They also had fewer pregnancies and deliveries and were more likely to use barrier contraception. Among STIs, Mycoplasma hominis demonstrated a significant association with HPV infection (adjusted OR = 2.16, 95% CI: 1.15–4.05, p = 0.017). Overall STI presence (adjusted OR = 2.16, p = 0.017) and STI multiplicity (adjusted OR = 1.36 per additional STI, p = 0.017) were also significantly associated with HPV positivity. Correlation analysis revealed a moderate association between Chlamydia trachomatis and Trichomonas vaginalis (ϕ = 0.39, p < 0.001), suggesting shared ecological or transmission pathways. Conclusion: The findings highlight the relevance of specific vaginal pathogens, particularly Mycoplasma hominis, and co-infection patterns in increasing the risk of HPV infection. These results underscore the importance of comprehensive STI screening and microbial profiling in cervical cancer prevention strategies, especially in populations with limited access to HPV vaccination. Further longitudinal and mechanistic studies are warranted to elucidate causal pathways and progression to cervical neoplasia. Full article

The presence of cetaceans along the Campania coast has always been documented. Between 2016 and 2022, out of 65 cetaceans stranded along the Campania coast, 46 were studied for bacteriological, virological, parasitological, and histopathological investigations. The results highlighted that for 59% (n = 27) of the specimens, the cause of death was of natural origin, while for only 2% (n = 1) of animals, the origin of death was ascribed to anthropic causes. Unfortunately, for 39% (n = 18) of the cetaceans, it was impossible to determine the cause of death. All the cetaceans that died of natural causes showed viral, bacterial, and parasitic infections. The primary pathogens detected were Cetacean Morbillivirus (CeMV, 65.2%, n = 30/46), Toxoplasma gondii (10.9%, n = 5/46), and Brucella ceti (8.7%, n = 4/46). The animals showed typical lesions of the isolated pathogens, such as systemic infection, meningoencephalitis, and pneumonia. Moreover, even with a lower frequency, other relevant pathogens like Photobacterium damselae, Salmonella enteritidis, Erysipelothrix rhusiopathiae, and Chlamydia abortus were isolated. These data were useful to understand the spread and circulation of these pathogens, some zoonotic, in the coastal marine waters of the Campania region. Full article

Cancer of the uterine cervix (cervical cancer) is a leading cancer among women worldwide, although its incidence has been reducing in many developing nations. In the majority of cervical cancer cases, the presence of high-risk human papillomavirus (HPV) is usually detected. However, a growing body of evidence currently considers that exclusive HPV infection may not be sufficient for cancer development. Apart from certain common risk factors for cervical cancer, like poor nutritional status and smoking, many studies documented an association with other viral infections, such as human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). Similarly, vaginal bacterial populations perhaps play a key role in cervical cancer. It may be worth mentioning that different bacterial species can immensely influence (either protecting or adversely) the biochemical characteristics of the cervicovaginal environment—for example, Lactobacillus crispatus, Gardnerella vaginalis, and Chlamydia trachomatis. As a result, chronic infections with unfavorable microorganisms (other than HPV) may affect the pathological processes of malignancy. On the other hand, the cervix is an estrogen-sensitive organ like the corpus uteri (i.e., the body of the uterus). Estrogen and different estrogen receptors are implicated in the development and promotion of various cancers, including endometrial cancer. A number of reports also suggest a close association between estrogen and HPV in the development of cervical cancer. Furthermore, estrogen is linked with the characteristics of the vaginal microenvironment including bacteria. Therefore, several of the abovementioned factors (some are preventable) could play an important role in the progression of cervical neoplastic lesions. Full article

Introduction: Sexual and reproductive health is a critical aspect of medical education, yet significant knowledge gaps persist even among future healthcare professionals. This study aimed to evaluate the knowledge, behaviors, and attitudes of Romanian medical students regarding sexually transmitted infections (STIs) and contraceptive practices. Materials and Methods: A cross-sectional observational study was conducted on 510 undergraduate medical students, using a validated 30-item online questionnaire assessing socio-demographic data, sexual behaviors, STI knowledge, and attitudes towards sexual health. Descriptive statistics, chi-square, and Spearman correlation tests were used to analyze the data. Results: Participants demonstrated a good understanding of common STI pathogens and transmission routes, with 99.02% identifying unprotected vaginal intercourse as a risk factor. However, only 58.82% correctly identified Chlamydia trachomatis, and awareness of less common pathogens remained low. Long-term complications such as infertility (85.29%) and cervical cancer (87.25%) were well recognized, although misconceptions about STI severity persisted, with over 40% believing that STIs are not dangerous because they are treatable. Male students reported earlier sexual debut and more frequent high-risk behaviors, while females were more likely to consult specialist doctors and receive HPV vaccination. The level of knowledge correlated positively with parental education and faculty program. Conclusions: Despite generally high awareness of STI-related topics, considerable gaps and misconceptions persist among Romanian medical students. These findings highlight the need for comprehensive, structured sexual health education integrated into medical curricula to ensure future healthcare providers are well-equipped to promote public health. Full article

Background/Objectives: Chlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and potential for serious health complications, no vaccine has been licensed. Pigs offer a valuable biomedical model for chlamydia research: they have an overall high degree of similarity to humans and serve as natural hosts for Chlamydia suis (Cs), a close relative of Ct. Thus, in this study, the pig model was used to evaluate a vaccine candidate against Ct. Methods: The vaccine candidate consists of chlamydial-protease-like activity factor (CPAF) protein adjuvanted with STING (Stimulator of Interferon Genes) pathway agonist cyclic-di-AMP (c-di-AMP). Pigs received two doses intramuscularly followed by two intranasal doses. Each week, the systemic T cell response was assessed via IFN-γ and IL-17 ELISpots, as well as multi-parameter flow cytometry on 0, 14, and 28 days post vaccination (dpv). The humoral immune response was analyzed by measuring CPAF-specific antibody levels and avidity via ELISAs. Results: Vaccination with c-di-AMP adjuvanted CPAF triggered low-level systemic IFN-γ and multifunctional IFN-γ⁺TNF-α⁺ CD4 T cell responses. Despite the rather low systemic effector cytokine production, robust anti-CPAF IgG responses were detected in serum, vaginal swab eluates, and oviduct flushes. Genital Ct challenge 42 dpv resulted in only transient infection, precluding a confident assessment of vaccine efficacy of the tested CPAF/c-di-AMP vaccine candidate. However, after challenge, vaccinated pigs exhibited boosted systemic anti-CPAF IFN-γ and mucosal IgG responses compared to unvaccinated pigs. Conclusions: Thus, while vaccine efficacy remains elusive, the CPAF/c-di-AMP vaccine candidate was immunogenic: it elicited a low-level systemic cell-mediated response and robust humoral immune responses. Future studies will incorporate a STING agonist directly conjugated to CPAF as well as addition of other Th1-inducing adjuvants to enhance cellular immunity. Full article

Background/Objectives: Inflammation, infections, and oxidative stress (OS) all have an impact on male infertility, which is a complicated, multifaceted illness. OS affects motility and fertilization capability. It accomplishes this through damaging sperm DNA, oxidizing proteins, and triggering lipid peroxidation. These effects occur due to an imbalance between reactive oxygen species (ROS) and antioxidant defenses. Methods: This review aims to evaluate the impact of oxidative stress and inflammation on male infertility by assessing recent literature. Results: Pro-inflammatory cytokines, like TNF-α and IL-6, interfere with spermatogenesis and promote oxidative damage. Additionally, infections caused by pathogens like Escherichia coli and Chlamydia trachomatis alter the reproductive microenvironment, leading to sperm dysfunction and inflammation. Conclusions: Early detection and targeted treatment are essential due to the intricate interactions among these elements. Microbiota-modulating techniques, antimicrobial therapies, anti-inflammatory drugs, and antioxidants are therapeutic approaches that may help reduce oxidative damage and enhance male fertility. Full article

Chlamydia trachomatis (Ct) is a leading cause of sexually transmitted infections globally, often resulting in inflammatory disorders, ectopic pregnancies, and infertility. Studying Ct’s pathogenesis remains challenging due to its unique life cycle and host-specific interactions, which require diverse experimental models. Animal studies using mouse, guinea pig, pig, and non-human primate models provide valuable insights into immune responses, hormonal influences, and disease progression. However, they face limitations in terms of translational relevance due to physiological differences, as well as ethical concerns. Complementing these, in vitro systems, ranging from simple monolayer to advanced three-dimensional models, exhibit improved physiological relevance by replicating the human tissue architecture. This includes the detailed investigation of epithelial barrier disruptions, epithelium–stroma interactions, and immune responses at a cellular level. Nonetheless, in vitro models fall short in mimicking the intricate tissue structures found in vivo and, therefore, cannot faithfully replicate the host–pathogen interactions or infection dynamics observed in living organisms. This review presents a comprehensive overview of the in vivo and in vitro models employed over the past few decades to investigate Ct and its pathogenesis, addressing their strengths and limitations. Furthermore, we explore emerging technologies, including organ-on-chip and in silico models, as promising tools to overcome the existing challenges and refine our understanding of Ct infections. Full article

Background/Objectives: Chlamydia trachomatis (Ct) is a common pathogen causing urogenital, anal, oral, and ocular infections. Although extensive vaccine efforts have been underway for decades, there is no licensed vaccine available to prevent human Ct infection. Polymorphic membrane protein D (PmpD) is a highly conserved protein present on the surface of Ct elementary bodies, suggesting an important role Ct biology. Repetitive tetrapeptide motifs GGA(I,L,V) and FxxN are conserved across Pmps and are important for adhesion in the related Chlamydia pneumoniae Pmp21. Methods: Using bioinformatics approaches, we identified amino acids 270 to 294 of PmpD that included two GGA(I,L,V) motifs and an FxxN motif as vaccine targets. Synthetic peptides corresponding to these regions were chemically conjugated separately via the carboxy (C)- or amino (N)-terminus (FxxN 1.1 and FxxN 1.2) to the surface of Qβ virus-like particles (VLPs) and were tested for immunogenicity and protective capacity in mice. Results: Female mice immunized three times with a mixture of Qβ-FxxN 1.1 and Qβ-FxxN 1.2 vaccines without exogenous adjuvant elicited geometric-mean endpoint dilution titers near 10⁴. Further, mice showed decreased infection at early time points when challenged vaginally with luciferase-expressing Chlamydia muridarum over 9 days and a faster time to undetectable infection compared to controls. Immunization with individual vaccines (Qβ-FxxN 1.1 or Qβ-FxxN 1.2) did not show the same degree of reduction. Conclusions: Vaccination against PmpD tetrapeptide motifs is a novel and promising approach for limiting initial Chlamydia infection and warrants further investigation to characterize the mechanism of protection. Full article

Over the past two decades, the global incidence of sexually transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis have increased significantly, particularly among cisgender men who have sex with men (MSM) and transgender women (TGW). This rise in STIs has spurred interest in new preventive measures, including doxycycline post-exposure prophylaxis (DoxyPEP). Clinical trials in the United States and France have demonstrated the effectiveness of DoxyPEP in reducing both chlamydia and syphilis incidence among MSM and TGW; although, its efficacy against gonorrhea remains limited, and it was further found to be ineffective among cisgender women in Kenya. Due to the promising results, the CDC and the German STI Society have incorporated DoxyPEP into their guidelines for specific high-risk groups. However, the broader implementation of DoxyPEP presents several challenges and ethical concerns. Key issues involve the potential development of antimicrobial resistance, particularly among common STI pathogens like C. trachomatis, M. genitalium, and N. gonorrhoeae, as well as other bacteria such as S. aureus and K. pneumoniae. Additionally, questions concerning equitable healthcare access, the potential impact on adherence to safer sex practices, and broader public health implications warrant careful consideration. Addressing these challenges necessitates a careful balance between the benefits and risks of DoxyPEP, as well as the implementation of strategies to mitigate negative outcomes while maximizing the impact on public health. Lastly, future research should explore the integration of DoxyPEP with other preventive strategies, such as vaccines, to enhance its effectiveness and reduce the global burden of STIs. Full article