Project Details
Abstract
Trichomoniasis is the most common sexually transmitted infection (STI) of non-viral origin in humans. The parasitic protozoan T. vaginalis adherent on the vaginal epithelial surface in females and elicit host innate and adaptive immune responses. Neutrophil is the predominant inflammatory cells found in the vaginal discharges of Trichomonas vaginitis. However, most infections still persist even under active host immune response. Moreover, T. vaginalis can secret Leukotriene B4 (LTB4), a potent stimulator of neutrophil chemotaxis. Obviously, the parasite has developed complex mechanisms to evade the host immune response. Previous studies mainly focus on the effects of parasite secretory molecules on immune cells. However, the real life biological interaction between T. vaginalis and host cells may involve factors originate from both sides. The ultimate goal of this proposal is to elucidate the cell-cell signaling network between T. vaginalis and host neutrophil.
In order to accomplish our goal, we already established an in-vitro co-culture system for T. vaginalis and neutrophil. Preliminary experimental data showed that this system can reproduce the response of neutrophil to T. vagianlis secretory products reported before. We will use this co-culture platform coupled with high-throughput proteomics and transcriptomics approaches to identify the effector molecules both in the parasite and neutrophil that associate with cell-cell communication.
Specifically, this three years proposal will aim to
(1) To identify the excretory secretory proteins (ESPs) profiles of T. vaginalis, neutrophil and co-culture system by using high-throughput LC/MS/MS system.
(2) To isolate and define the content of exosome spread by T. vaginalis and neutrophil.
(3) To reveal the alternations of RNA expression patterns of T. vaginalis and neutrophil co-culture by using next-generation sequencing
(4) To classify the contact-dependent and -independent responses of T. vaginalis to neutrophil.
(5) To investigate the roles of identified molecules in the communication of neutrophil to T. vaginalis.
Experimental results from the present proposal will help to illustrate the cross-talks between T. vaginalis and neutrophil. The gene expression profile of T. vaginalis will provide a novel insight into the consequent responses after encountered with neutrophil, and vice versa. Moreover, the identification of ESPs and exosome in the co-culture supernatant will help us to define the indirect communicating molecules that affect each other. These regulatory mechanisms will enhance our understanding on the colonization and survival of T. vaginalis under threats of host immune cells and potentially used as a basis for the development of new chemotherapeutic strategy and diagnostic kits.
Project IDs
Project ID:PC10901-0666
External Project ID:MOST107-2320-B182-021-MY3
External Project ID:MOST107-2320-B182-021-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/20 → 31/07/21 |
Keywords
- Trichomonas vaginalis
- neutrophil
- cell-cell signaling.
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