# Identification of key players mediating internalization of Trichomonas vaginalis extracellular vesicles by host cells and parasite adherence and survival in vivo

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $655,957

## Abstract

Project Summary/Abstract
The unicellular parasite Trichomonas vaginalis is responsible for the most prevalent, non-viral, sexually-
transmitted infection worldwide, with approximately ¼ billion people contracting trichomoniasis annually.
Trichomoniasis is the most common parasitic infection in the US, with an annual incidence estimated at ~5 million
cases. Nevertheless, this parasite is vastly understudied. As such, T. vaginalis was classified by the Center of
Disease Control and Prevention as a neglected infection in the US in 2014. In addition to being a common cause
of vaginitis, trichomoniasis is associated with adverse inflammatory sequelae, that can contribute to pregnancy
complications and neonatal mortality, the spread of HIV, and increased metastasis of urogenital cancers. The
incidence of infection, the growing recognition that T. vaginalis is associated with long-term health consequences
and an increase in the number of drug resistant clinical isolates of T. vaginalis underscore the need to develop
new chemotherapeutic and vaccine design strategies. A much better understanding of processes involved in
infectivity and pathogenesis, such as those proposed here, will be imperative to achieve these goals. Several
years ago we discovered that T. vaginalis secretes small, membrane-bound extracellular vesicles (EVs), that
mediate host:parasite interactions. We have shown that parasite proteins are transferred to host cells via EVs,
which in turn, modulates both parasite adherence to host cells and the host cell responses. Host:pathogen cross-
talk mediated by EVs likely contributes to parasite colonization of the host and down-regulation of cytokines that
elicit immune cells to the site of infection. This proposal focuses on the molecular and cellular mechanisms used
for host cell internalization of EVs: a process required for EV-mediated communication between the parasite and
host. We will also examine the effect of EVs on the survival of parasites in vivo using a newly-developed mouse
model. To this end, we propose to: characterize biochemical properties of an EV ligand (Tv 4-alpha-
glucanotransferase) that binds host cell heparan sulfate proteoglycans and drives EV internalization by host cells
(Aim 1); isolate and identify EV receptor(s) on the host cell and test whether the receptor(s) are required for EV
internalization (Aim 2) and to identify EV proteins involved in host cell internalization and test whether EVs affect
parasite survival during early stage infection in vivo using isogenic T. vaginalis strains that differ in host cell
adherence (Aim 3). We will uncover biochemical and cellular mechanisms that promote parasite infection and
will reveal whether our in vitro findings supporting a role for EVs in host cell colonization are confirmed in vivo.
Novel mechanisms are likely to be found, as very little mechanistic data on the interaction or uptake of any
parasite-derived EV with host cells have been reported. In addition to expand...

## Key facts

- **NIH application ID:** 10070475
- **Project number:** 1R01AI148475-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patricia Jean Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $655,957
- **Award type:** 1
- **Project period:** 2020-06-02 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070475

## Citation

> US National Institutes of Health, RePORTER application 10070475, Identification of key players mediating internalization of Trichomonas vaginalis extracellular vesicles by host cells and parasite adherence and survival in vivo (1R01AI148475-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070475. Licensed CC0.

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