Role of cytoneme structures and extracellular vesicles in Trichomonas vaginalis parasite-parasite communication

Abstract

Trichomonas vaginalis, the etiologic agent of the most common non-viral sexually transmitted infection worldwide, colonizes the human urogenital tract where it remains extracellular and adheres to epithelial cells. With an estimated annual prevalence of 276 million new cases, mixed infections with different parasite strains are expected. Although it is considered as obvious that parasites interact with their host to enhance their own survival and transmission, evidence of mixed infections call into question the extent to which unicellular parasites communicate with each other. Here, we demonstrated that different T. vaginalis strains can communicate through the formation of cytoneme-like membranous cell connections. We showed that T. vaginalis adherent strains form abundant membrane protrusions and cytonemes formation of an adherent parasite strain (CDC1132) is affected in the presence of a different strain (G3 or B7RC2). Using cell culture inserts assays, we demonstrated that the effect in cytoneme formation is contact-independent and that extracellular vesicles (EVs) are responsible, at least in part, of the communication among strains. We found that EVs isolated from G3, B7RC2, and CDC1132 strains contain a highly distinct repertoire of proteins, some of them involved in signaling and communication, among other functions. Finally, we showed that parasite adherence to host cells is affected by this communication between strains as binding of adherent T. vaginalis CDC1132 strain to prostate cells is significantly higher in the presence of G3 or B7RC2 strains. Demonstrating that interaction of isolates with distinct phenotypic characteristics may have significant clinical repercussions, we also observed that a poorly adherent parasite strain (G3) adheres more strongly to prostate cells in the presence of an adherent strain. The study of signaling, sensing, and cell communication in parasitic organisms will surely enhance our understanding of the basic biological characteristics of parasites, which may have important consequences in pathogenesis.

Trichomonas vaginalis: Monolayer and Cluster Formation—Ultrastructural Aspects Using High-Resolution Scanning Electron Microscopy

“…In addition, it has been reported that cytonemes are associated with clump formation [34] and that highly adherent strains aggregate more than poorly adherent strains [18,34,35]. The authors demonstrated that different parasites inside the clumps are connected by cytonemes, which are longer filopodia extensions reaching up to ~300 nm from the originating cell body [34]. The authors reported that interaction between different strains induced cytoneme formation [36] and that parasite clumping is strain-dependent.…”

“…One group [18] claimed that TvTSP8 from the Tetraspanin family (TvTSPs) was involved in parasite aggregation, suggesting a role for this protein in parasite interaction. In addition, it has been reported that cytonemes are associated with clump formation [34] and that highly adherent strains aggregate more than poorly adherent strains [18,34,35]. The authors demonstrated that different parasites inside the clumps are connected by cytonemes, which are longer filopodia extensions reaching up to ~300 nm from the originating cell body [34].…”

Exosome‐derived long noncoding RNAs: Mediators of host–Plasmodium parasite communication

“…falciparum (Khowawisetsut et al, 2023), Leishmania (Weber et al, 2023), T . cruzi (Cornet‐Gomez et al, 2023), Echinococcus multilocularis (Liu et al, 2023), and Giardia intestinalis (Salas et al, 2023), secrete EVs containing an assortment of bioactive molecules, including lipids, proteins, glycans, DNA, and RNA during infections (Chen et al, 2023; Gutierrez et al, 2022; Szempruch et al, 2016). These EVs serve as an efficient delivery system, transferring bioactive signals to target cells (Ofir‐Birin & Regev‐Rudzki, 2019; Szempruch et al, 2016).…”

“…EVs play a critical role as mediators of intercellular communication in the interaction between parasites and their hosts or among parasites themselves (Mantel & Marti, 2014;Marcilla et al, 2014;Mardahl et al, 2019;Ofir-Birin et al, 2017). Multiple parasitic pathogens, such as P. falciparum (Khowawisetsut et al, 2023), Leishmania (Weber et al, 2023), T.cruzi (Cornet-Gomez et al, 2023), Echinococcus multilocularis (Liu et al, 2023), and Giardia intestinalis (Salas et al, 2023), secrete EVs containing an assortment of bioactive molecules, including lipids, proteins, glycans, DNA, and RNA during infections (Chen et al, 2023;Gutierrez et al, 2022;Szempruch et al, 2016). These EVs serve as an efficient delivery system, transferring bioactive signals to target cells (Ofir-Birin & Regev-Rudzki, 2019;Szempruch et al, 2016).…”

Learning the language of pathogens

“…Now, in eLife, Natalia de Miguel (Instituto Tecnológico Chascomús and Escuela de Bio y Nanotecnologías) and colleagues – including Nehuén Salas and Manuela Blasco Pedreros as joint first authors – report that different strains of the protozoan Trichomonas vaginalis , a parasite responsible for sexually-transmitted infections, communicate using extracellular vesicles and a type of filopodia called a cytoneme ( Salas et al, 2023 ). Cytonemes are thin specialized filopodia that can traffic signalling proteins ( Roy and Kornberg, 2015 ).…”