Trichomonas vaginalis induces IL-1ß production in a human prostate epithelial cell line by activating the NLRP3 inflammasome via reactive oxygen species and potassium ion efflux.

BACKGROUND: Trichomonas vaginalis is a sexually transmitted protozoan parasite that causes vaginitis in women, and urethritis and prostatitis in men. IL-1ß is synthesized as immature pro-IL-1ß, which is cleaved by activated caspase-1. Caspase-1 is, in turn, activated by a multi-protein complex known as an inflammasome. In this study, we investigated the inflammatory response of a prostate epithelial cell line (RWPE-1) to T. vaginalis and, specifically, the capacity of T. vaginalis to activate the NLRP3 inflammasome. METHODS: RWPE-1 cells were stimulated by live T. vaginalis, and subsequent expression of pro-IL-1ß, IL-1ß, NLRP3, ASC and caspase-1 was determined by real-time PCR and Western blotting. IL-1ß and caspase-1 production was also measured by ELISA. To evaluate the effects of NLRP3 and caspase-1 on IL-1ß production, the activated RWPE-1 cells were transfected with small interfering RNAs to silence the NLRP3 and caspase-1 genes. Activation of the NLRP3 inflammasome was observed by fluorescence microscopy. Intracellular reactive oxygen species (ROS) were evaluated by spectrofluorometry. RESULTS: When RWPE-1 cells were stimulated with live T. vaginalis, the mRNA and protein expression of IL-1ß, NLRP3, ASC, and caspase-1 increased. Moreover, silencing of NLRP3 and caspase-1 attenuated T. vaginalis-induced IL-1ß secretion. The NADPH oxidase inhibitor DPI and high extracellular potassium ion suppressed the production of IL-1ß, caspase-1, and the expression of NLRP3 and ASC proteins. The specific NF-κB inhibitor, Bay 11-7082, inhibited IL-1ß production, and also inhibited the production of caspase-1, ASC and NLRP3 proteins. CONCLUSIONS: T. vaginalis induces the formation of the NLRP3 inflammasome in human prostate epithelial cells via ROS and potassium ion efflux, and this results in IL-1ß production. This is the first evidence for activation of the NLRP3 inflammasome in the inflammatory response by prostate epithelial cells infected with T. vaginalis. Prostate 76:885-896, 2016. © 2016 Wiley Periodicals, Inc.

Male accessory gland infection and sperm parameters (review).

Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males (Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate-vesiculitis and prostate-vesiculo-epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non-conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub-obstruction of the seminal tract.

Impact of T. vaginalis infection on innate immune responses and reproductive outcome.

Trichomonas vaginalis is the most common non-viral sexually transmitted pathogen. The infection is prevalent in reproductive age women and is associated with vaginitis, endometritis, adnexitis, pyosalpinx, infertility, preterm birth, low birth weight, bacterial vaginosis, and increased risk of cervical cancer, HPV, and HIV infection. In men, its complications include urethritis, prostatitis, epididymitis, and infertility through inflammatory damage or interference with the sperm function. The infection is often asymptomatic and recurrent despite the presence of specific antibodies, suggesting the importance of the innate immune defense. T. vaginalis adhesion proteins, cysteine proteases, and the major parasite lipophosphoglycan (LPG) play distinct roles in the pathogenesis and evasion of host immunity. LPG plays a key role in the parasite adherence and signaling to human vaginal and cervical epithelial cells, which is at least in part mediated by galectins. The epithelial cells respond to T. vaginalis infection and purified LPG by selective upregulation of proinflammatory mediators. At the same time, T. vaginalis triggers an immunosuppressive response in monocytes, macrophages, and dendritic cells. The molecular mechanisms underlying reproductive complications and epidemiologic risks associated with T. vaginalis infection remain to be elucidated.

Association between trichomoniasis and bacterial vaginosis: examination of 600 cervicovaginal smears.

To determine whether there is a relationship between trichomoniasis and bacterial vaginosis (BV), cervicovaginal smears obtained from 600 women were stained with the Papanicolaou technique and examined cytologically. Thirty-six (6%) of 600 women were diagnosed as having Trichomonas vaginalis [TV(+)]. Sixteen (44.4%) of 36 TV(+) cases were observed as having BV [BV(+)]. Thirty-one of 564 TV(-) vaginal smears were also positive for BV (5.5%). There was a statistically significant correlation between trichomoniasis and bacterial vaginosis (p < 0.05). It is possible that TV might create an anaerobic environment, thereby changing the vaginal flora. This flora becomes a more suitable milieu for growing of anaerobic microorganisms. It can be postulated that TV might be the most important protozoan that contributes to the overgrowth of BV-related microorganisms.

[Pulmonary trichomoniasis: diagnosis based on identification of irritation in bronchoalveolar lavage]. / Pulmonale Trichomoniasis: Diagnose durch Erregernachweis in der bronchoalveolären Lavage.

Bronchopulmonary infections caused by trichomonads have been reported mainly in patients with pre-existing pulmonary or debilitating disease (e.g. bronchial carcinoma, lung abscess, bronchiectasis). Pulmonary trichomoniasis is most often due to infection with Trichomonas tenax, usually regarded as a harmless commensal of the human mouth, and may rarely be caused by other trichomonas species. A 45 year old female presented with a dry cough, exertional dyspnoea and malaise. These symptoms persisted for 6 months regardless of anti-inflammatory and anti-obstructive inhalative therapy. Sarcoidosis of the lungs, diagnosed 20 years prior, had been asymptomatic since and there was no coexistent disease. Laboratory data revealed increased ACE-levels (90 IE/ml) and lung function showed bronchial hyperreactivity on histamine challenge. No other abnormalities were found (chest x-ray, bronchoscopy, lung function test, blood count and serum calcium). The diagnosis was based on the cytological identification of numerous trophozoites of T. tenax in the bronchoalveolar lavage. Therapy with oral metronidazol for 40 days led to complete recovery from symptoms and normalisation of ACE serum levels. The patient has remained well for 12 months since. The pathogenicity of oral trichomonads in the non-immunocompromised host remains uncertain. Our patient had no known medical risk factors by comparison with published cases. The case illustrates the clinical relevance of pulmonary trichomoniasis in an otherwise healthy person.

Pathogenicity of a strain of Trichomonas gallinarum in turkeys and its possible interaction with cecal coccidia.

The pathogenicity of Trichomonas gallinarum (TG) in turkeys and chickens was assessed in a series of four experiments. TG was shown to be resistant to freezing for a period of 1 hr at -20 C; birds administered an emulsion of previously frozen TG were readily infected. Young birds receiving this inoculum were more likely to be infected with TG in both ceca compared with birds administered TG emulsion that had remained at room temperature for the same length of time. In this and other experiments, birds infected with the parasite consistently produced a yellow frothy liquid in the ceca, as well as small raised papulae on the mucosal surface of the ceca. Histologically, the lesions were located in the lamina propria, with openings that extended from the apex of the lesion to the crypts. The lamina propria was consistently infiltrated by lymphocytes and scattered heterophiles. Although TG is likely involved in the pathogenesis of the lesions, the resulting pathology could not be linked definitively to TG alone because inoculation was performed with a cecal contents homogenate containing significant numbers of cecal bacteria. Combined infections of TG and Eimeria adenoides (EA) were also studied. Turkeys administered both parasites were more frequently infected with TG in both ceca compared with those that received TG alone. Ceca infected with TG alone tended to be enlarged and gas filled, whereas those infected with the combination of TG and EA were smaller and usually lacked the yellow frothy liquid contents.

Vaginal discharge. Its causes and cures.

Vaginal discharge is a common complaint, the cause of which can be diagnosed on the basis of the distinguishing characteristics of the fluid itself, the course and symptoms of the infection, and the results of a few simple office laboratory tests. Accurate diagnosis is important because treatment can then be selected specifically rather than empirically. Optimal treatment differs with each of the four major causative agents: Candida, Gardnerella, Trichomonas, and Chlamydia. Prompt eradication of the infection promotes patient and public health.