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

https://doi.org/10.1016/j.jri.2009.08.007Get rights and content

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.

Section snippets

Unique features of T. vaginalis: more than 170 years of history

Trichomonas 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

Clinical manifestations and impact on reproductive health

In women T. vaginalis causes a wide spectrum of symptoms, ranging from a relatively asymptomatic state to severe inflammation and irritation with foul-smelling vaginal discharge, low abdominal pain, and dysuria. The associated morbidities and complications include vaginitis, endometritis, adnexitis, pyosalpinx, atypical pelvic inflammatory disease, preterm birth, premature membrane rupture, low birth weight, infertility, cervical cancer, enhanced risk of HIV-1 and other viral infections, and a

Alarming epidemiologic trends

Worldwide 160–180 million people are infected with T. vaginalis each year, and of those 154 million are in resource-limited settings; 8–10 million are in the United States and 11 million are in Europe (McClelland, 2008). The incidence of T. vaginalis infection occurs more than Chlamydia and gonorrhea put together. In the United States the prevalence among women ranges from 2.8% in adolescents nationwide to 51% in some black communities (Shafir et al., 2009). In men statistics is less reliable

Immunoinflammatory responses to T. vaginalis infection in pregnant women

The immunoinflammatory response to trichomoniasis has been most studied in pregnant women. T. vaginalis positive pregnant women with bacterial vaginosis (Nugent 7-10) had increased vaginal IL-1β and neutrophils compared with bacterial vaginosis alone (Cauci and Culhane, 2007). Increased cervical IL-8 and alpha-defensin have been found in pregnant infected women (Simhan et al., 2007). At the same time in symptomatic women, anti-inflammatory mediators such as the soluble leukocyte protease

Modeling the infection and immunity in vivo and in vitro

The immunoinflammatory responses to T. vaginalis infection have been studied in vitro and in mouse models. In vitro experimentation has been conducted with cervical and vaginal epithelial cells (Bastida-Corcuera et al., 2005, Fichorova et al., 2006, Kucknoor et al., 2005a, Kucknoor et al., 2005b, Kucknoor et al., 2007, Okumura et al., 2008, Singh et al., 2009, Sommer et al., 2005), and with various immune cell types (Chang et al., 2006a, Chang et al., 2004, Ryu et al., 2004, Shaio et al., 1995

The T. vaginalis lipophosphoglycan—functional domains and innate immunity mechanisms

The T. vaginalis lipophosphoglycan (LPG) has become the focus of extensive studies ever since it was discovered that it is the most abundant glycoconjugate on the parasite surface (2–3 × 106 copies/parasite) and is responsible for the parasite adherence to the vaginal epithelial cells (Singh et al., 2007). It is a pure carbolipid (no peptide component) anchored on the parasite surface via inositol-phosphoceramide. Unlike LPG from other parasites (Leishmania), Trichomonas LPG does not undergo

Future directions

Future studies are needed to identify the host receptors and the host's as well as parasite's pathways involved in the symptomatic and asymptomatic sequelae and immune evasion by T. vaginalis. The mechanisms of the synergistic interactions between T. vaginalis and bacterial vaginosis, the most common vaginal syndrome of reproductive age women, are virtually unknown. More research is needed to understand and prevent the negative impact of T. vaginalis on women's reproductive health and the risk

Acknowledgments

The work on T. vaginalis immunobiology in the author's laboratory has been supported by NIH/NICHD grants R21HD054451-01 and R21HD054451-02 with continued support by NIH/NIAID R01AI079085-01A2. The author would like to acknowledge the collaboration of her laboratory with the laboratories of Dr. B.N. Singh (SUNY Upstate Medical University, NY, USA), and Dr. C. Costello (Boston University School of Medicine, MA, USA), which have played a significant role in elucidating the molecular structure and

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