PXD021696

PXD021696 is an original dataset announced via ProteomeXchange.

Title	The role of exosomes in viral-protozoan symbiosis: lessons from Trichomonasvirus in an isogenic host parasite model
Description	The protozoan parasite Trichomonas vaginalis (TV), exclusively adapted to the human genital tract, is one of the most common sexually transmitted pathogens. Adding to the complexity of the host-pathogen interactions, the parasite harbors TV-specific endosymbiont viruses (Trichomonasvirus, TVV). It was reported that small extracellular vesicles (exosomes) released by TV play a role in host immunity; however, the role of the viral endosymbiosis in this process remained unknown. We hypothesized that the virus may offer evolutionary benefit to its protozoan host at least in part by altering the immunomodulatory properties of exosomes spreading from the site of infection to non-infected immune effector cells. We infected human vaginal epithelial cells, the natural host of the parasite, with TV natively harboring TVV and an isogenic derivative of the parasite cured from the viral infection. Exosomes were isolated from vaginal cell culture 24 h post TV infection and from medium where the isogenic TV strains were cultured in the absence of the human host. Exosomes from TVV-negative but not TVV-positive parasites cultured alone caused NF-kB activation and increase of IL-8 and RANTES expression by uterine endocervical cells, which provide innate immune defense at the gate to the upper reproductive tract. Similarly, mononuclear leukocytes increased their IL-8, IL-6 and TNF-a output in response to exosomes from virus-negative, but not isogenic virus-positive parasites, the latter exosomes being immunosuppressive in comparison to TV medium control. The same phenomenon of suppressed immunity induced by the TVV-positive compared to TVV-negative phenotype was seen when stimulating the leukocytes with exosomes originating from infected vaginal cultures. In addition, the exosomes from the TVV-positive infection phenotype suppressed immune signaling of a toll-like receptor ligand derived from mycoplasma, another frequent TV symbiont. Quantitative comparative proteome analysis of exosomes from viruspositive versus virus-negative TV revealed differential expression of two functionally uncharacterized proteins and five proteins involved in Zn binding, protein binding, electron transfer, transferase and catalytic activities. These data support the concept that symbiosis with viruses may provide benefit to the protozoan parasite by exploiting exosomes as a vehicle for inter-cellular communications and modifying their protein cargo to suppress host immune activation.
HostingRepository	MassIVE
AnnounceDate	2020-10-07
AnnouncementXML	Submission_2020-10-07_06:54:34.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Bogdan Budnik
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Saccharomycetales; common name: budding yeasts; NCBI TaxID: 4892; scientific name: Trichomonas vaginalis; NCBI TaxID: 5722;
ModificationList	Oxidation; Deamidated; TMT6plex
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-25 15:49:49	ID requested
⏵ 1	2020-10-07 06:54:34	announced

no publication

submitter keyword: Trichomonasvirus, T. vaginalis, Exosomes, extracellular vesicles, Immune Modulation, Cytokines

Raina N. Fichorova
contact affiliation	Harvard Medical School, Brigham and Womens Hospital
contact email	rfichorova@bwh.harvard.edu
lab head
Bogdan Budnik
contact affiliation	Harvard University
contact email	bbudnik@mcb.harvard.edu
dataset submitter

MassIVE dataset URI

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