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

Abstract

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. KeywordsTrichomonas vaginalis; lipophosphoglycan; cytokines; galectins; human vaginal epithelial cells Unique features of T. vaginalis: more than 170 years of historyT. vaginalis is a sexually transmitted extracellular flagellated single-cell parasite that lives in the female lower reproductive tract and the male urethra. Unique genetic and structural features place the parasite at the base of the eukaryotic phylogenetic tree and suggest an intriguing evolution toward mucosal parasitism. T. vaginalis selectively adheres to the human vaginal epithelial cells, surviving for years in the hostile vaginal environment that is typically acidic, contains a plethora of microbicidal innate immune factors, and is reinforced by the presence of a complex commensal bacterial consortium.T. vaginalis was first recorded in the medical literature more than 170 years ago by a European physician, Alfred Done, who described the trichomonad in human vaginal discharge in 1836.

Regulation of Nuclear Translocation of the Myb1 Transcription Factor by TvCyclophilin 1 in the Protozoan Parasite Trichomonas vaginalis

“…The parasitic protozoan Trichomonas vaginalis is the most common cause of nonviral sexually transmitted diseases of humans (1). The infection usually manifests mild symptoms or is asymptomatic, but it can cause adverse events during pregnancy that range from low birth weight at birth to abortion and stillbirth (2).…”

“…Curative chemotherapy is available, but transmission is difficult to control, and reports on clinical drug-resistant isolates have been increasing in recent years (2,3). Upon infection, the parasite trophozoites can breach the mucosal and epithelial barriers, lyse red blood cells, degrade complements and other humoral factors in host defense, and elicit chronic inflammation (1,4). The infection has also been linked to the elevated transmission of human immunodeficiency virus (HIV) and human papillomaviruses (1,3,5,6), making this overlooked pathogen a threat to public health.…”

Investigation of the presence of Trichomonas vaginalis in infertile Turkish women

“…Increased levels of IgA, IgG, Th1 cytokines and reactive nitrogen intermediates were observed in rats having experimentally induced T. vaginalis [8,21]. Antibodies against T. vaginalis were detected in circulation and vaginal mucosa of infected women [8,22,23].…”

“…Antibodies against T. vaginalis were detected in circulation and vaginal mucosa of infected women [8,22,23]. T. vaginalis cysteine proteases including CP30 may induce apoptosis of vaginal epithelial cells and multiple mucosal immune cell types [8,24]. These immunological changes may be a cause of infertility.…”

“…Although this method is inexpensive and fast, sensitivity is not high and the parasite is detected in only 60% of culture positive samples. Novel diagnostic methods such as nucleic acid amplification are more sensitive than routine diagnostic methods, but more expensive and not generally available [7,8].…”