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TMT analysis reveals the immuno-modulation of exosomes in Zhikong scallop Chlamys farreri

ABSTRACT: As marine invertebrates, scallops lack adaptive immunity and employ innate immunity as the front line and almost the solo defense mechanism to protect them against invaders. Accumulating research achievements demonstrated that exosomes could act as innate immune effectors that contribute to host defense mechanism. To better understand the immune functions of exosomes in Chlamys farreri, proteomics feature of hemocytes from scallops injected with PBS, with normal exosomes and LPS stimulating exosomes, respectively, were generated by TMT analysis, in triplicate.

ORGANISM(S): Azumapecten Farreri

SUBMITTER: Mengqiang Wang

PROVIDER: PXD016755 | iProX | Sat Dec 14 00:00:00 GMT 2019

REPOSITORIES: iProX

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Project 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.

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TMT analysis reveals the immuno-modulation of exosomes in Zhikong scallop Chlamys farreri

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