Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence

Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.

High prevalence of sexually transmitted infections and risk factors among HIV-positive individuals in Yunnan, China

Background Yunnan has the highest rates of HIV in China. Other treatable sexually transmitted infections (STIs) are associated with accelerated HIV transmission and poor ART outcomes, but are only diagnosed by syndromic algorithms. Methods We recruited 406 HIV-positive participants for a cross-sectional study (204 ART-naive and 202 receiving ART). Blood samples and first-voided urine samples were collected. Real-time polymerase chain reaction methods were used for diagnosing Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and Mycoplasma genitalium (MG). Syphilis and herpes simplex virus type 2 (HSV-2) tests were also performed. Results Among the 406 participants, the overall prevalence of STIs was 47.0% and 45.1% in ART-naive individuals and 49.0% in individuals receiving ART, respectively. The testing frequencies were 11.6% (11.8% vs. 11.4%), 33.2% (29.4% vs. 37.1%), 3.2% (3.4% vs. 3.0%), 2.0% (3.4% vs. 0.5%) and 4.7% (6.4% vs. 3.0%) for active syphilis, HSV-2, CT, NG and MG, respectively. The percentage of multiple infections in both groups was 10.8% (22/204) in ART-naive participants and 9.9% (20/202) in participants receiving ART. Female sex, an age between 18 and 35 years, ever injecting drugs, homosexual or bisexual status, HIV/HBV coinfection, and not receiving ART were identified as risk factors. Self-reported asymptomatic patients were not eliminated from having a laboratory-diagnosed STI. Conclusions The STI prevalence was 47.0% (45.1% vs. 49.0%), and HSV-2, syphilis and MG were the most common STIs in HIV-infected individuals. We found a high prevalence (6.4%) of MG in ART-naive individuals. HIV-positive individuals tend to neglect or hide their genital tract discomfort; thus, we suggest strengthening STI joint screening and treatment services among HIV-infected individuals regardless of whether they describe genital tract discomfort.

Immunogenicity and Protective Capacity of a Virus-like Particle Vaccine against Chlamydia trachomatis Type 3 Secretion System Tip Protein, CT584

An effective vaccine against Chlamydia trachomatis is urgently needed as infection rates continue to rise and C. trachomatis causes reproductive morbidity. An obligate intracellular pathogen, C. trachomatis employs a type 3 secretion system (T3SS) for host cell entry. The tip of the injectosome is composed of the protein CT584, which represents a potential target for neutralization with vaccine-induced antibody. Here, we investigate the immunogenicity and efficacy of a vaccine made of CT584 epitopes coupled to a bacteriophage virus-like particle (VLP), a novel platform for Chlamydia vaccines modeled on the success of HPV vaccines. Female mice were immunized intramuscularly, challenged transcervically with C. trachomatis, and assessed for systemic and local antibody responses and bacterial burden in the upper genital tract. Immunization resulted in a 3-log increase in epitope-specific IgG in serum and uterine homogenates and in the detection of epitope-specific IgG in uterine lavage at low levels. By contrast, sera from women infected with C. trachomatis and virgin controls had similarly low titers to CT584 epitopes, suggesting these epitopes are not systemically immunogenic during natural infection but can be rendered immunogenic by the VLP platform. C. trachomatis burden in the upper genital tract of mice varied after active immunization, yet passive protection was achieved when immune sera were pre-incubated with C. trachomatis prior to inoculation into the genital tract. These data demonstrate the potential for antibody against the T3SS to contribute to protection against C. trachomatis and the value of VLPs as a novel platform for C. trachomatis vaccines.

Evidence for cGAS-STING signaling in the female genital tract resistance to Chlamydia trachomatis infection

Sexually transmitted Chlamydia trachomatis can ascend to the upper genital tract due to its resistance to innate immunity in the lower genital tract. C. trachomatis can activate cGAS-STING signaling pathway in cultured cells via either cGAS or STING. The current study was designed to evaluate the role of the cGAS-STING pathway in innate immunity against C. trachomatis in the mouse genital tract. Following intravaginal inoculation, C. trachomatis significantly declined by day 5 following a peak infection on day 3 while the mouse-adapted C. muridarum continued to rise for >1 week, indicating that C. trachomatis is susceptible to the innate immunity in the female mouse genital tract. This conclusion was supported by the observation of a similar shedding course in mice deficient in adaptive immunity. Thus, C. trachomatis can be used to evaluate innate immunity in the female genital tract. It was found that mice deficient in either cGAS or STING significantly increased the yields of live C. trachomatis on day 5, indicating an essential role of the cGAS-STING signaling pathway in innate immunity of the mouse genital tract. Comparison of live C. trachomatis recovered from different genital tissues revealed that the cGAS-STING-dependent immunity against C. trachomatis was restricted to the mouse lower genital tract regardless of whether C. trachomatis was inoculated intravaginally or transcervically. Thus, we have demonstrated an essential role of the cGAS-STING signaling pathway in innate immunity against chlamydial infection, laying a foundation for further illuminating the mechanisms of the innate immunity in the female lower genital tract.

Evaluation of the recurrence and fertility rate following salpingostomy in patients with tubal ectopic pregnancy

Background Ectopic pregnancy is one of the leading causes of pregnancy-related mortality; the treatment strategies associated with this condition entail complications, such as recurrence of ectopic pregnancy or infertility. The objective of this study was to evaluate the recurrence and fertility rate after salpingostomy in patients with tubal ectopic pregnancy. Methods This cross-sectional retrospective study was conducted at four referral centers of Obstetrics and Gynecology, under the supervision of Shiraz University of Medical Sciences (Iran). The medical records of 125 patients with tubal pregnancy were reviewed. These patients underwent laparoscopic salpingostomy from April 2009 to March 2016.Data on maternal age, BMI, history of previous EP, genital tract infection, IUD insertion, history of previous surgery, and infertility were further obtained. The patients were followed up for approximately 1 to 7 years. The recurrence of EP and subsequent pregnancy rate were assessed during the follow-up period. Results There was no statistically significant relationship between post-salpingostomy recurrence and maternal age, previous abdominopelvic surgery, and history of infertility(P = .425); however, the post-salpingostomy recurrence of EP was correlated with BMI (P = 0.001), previous history of EP (P = 0.001), genital tract infection (P = 0.001), and IUD insertion (P = 003). Among 95 women who had no contraception, pregnancy occurred in 51 cases (53.6%) and recurrence of EP was observed in 16 patients (12.8%). Conclusions Our results suggest that salpingostomy is a safe method with a low risk of recurrence and good fertility outcomes for women who consider future pregnancy.

The Endometrial Microbiome and Its Impact on Human Conception

Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.

Influence of cow reproductive tract microbiota on formation of calf upper respiratory tract microbiota

Diagnosis of latent endometritis and predicting the effect of the inflammatory process on the course of pregnancy and its outcome is a necessary measure when conducting clinical examination of animals. Lack of diagnostic criteria, including microbiological one, cause difficulties for veterinarians in assessing latent endometritis. Often, animals suffering from latent inflammation of the reproductive tract are infertile and cannot be treated. And from cows with dysbiosis of the genital tract, sick young animals are born, lagging behind in growth and development. The aim of the work was to establish the relationship between the genital tract microbiome, the number and species composition of commensals and opportunistic microorganisms on the ability to carry pregnancy. Washes from the oral and nasal cavities were taken from the young born to study the microbiome: lactic acid microorganisms in combination with opportunistic pathogens. As a result of the research, it was found that animals with a low number of lactic acid microorganisms and an increased titer of opportunistic microorganisms were infertile, which led to their culling. In young animals, they are present in the respiratory tract in all samples, together with coccal microorganisms. The study of lactic acid microorganisms is advisable in the diagnosis of inflammatory processes of the reproductive tract and upper respiratory tract.