Schistosomal extracellular vesicle-enclosed miRNAs modulate host T helper cell differentiation

Tal Meningher, Yiftah Barsheshet, Yifat Ofir-Birin, Daniel Gold, Boris Brant, Elya Dekel, Yechezkel Sidi, Eli Schwartz*, Neta Regev-Rudzki, Orly Avni, Dror Avni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti-parasitic type 2 helper T-cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen-presenting cell-independent manner, by modulating the Th2-specific transcriptional program. Adult schistosomes secrete miRNA-harboring extracellular vesicles that are internalized by Th cells in vitro. Schistosomal miRNAs are found also in T helper cells isolated from Peyer's patches and mesenteric lymph nodes of infected mice. In T helper cells, the schistosomal miR-10 targets MAP3K7 and consequently downmodulates NF-κB activity, a critical transcription factor for Th2 differentiation and function. Our results explain, at least partially, how schistosomes tune down the Th2 response, and provide further insight into the reciprocal geographic distribution between high prevalence of parasitic infections and immune disorders such as allergy. Furthermore, this worm-host crosstalk mechanism can be harnessed to develop diagnostic and therapeutic approaches for human schistosomiasis and Th2-associated diseases.

Original languageEnglish
Article numbere47882
JournalEMBO Reports
Volume21
Issue number1
DOIs
StatePublished - 7 Jan 2020

Funding

FundersFunder number
Benoziyo Endowment Fund for the Advancement of Science
D.A.
E.S.
European?Union's Horizon 2020 research and innovation program
Israeli Ministry of industry52698
Jeanne?and Joseph Nissim Foundation for Life Sciences Research
Soref Foundation
Weizmann Institute of Science?Sheba Medical Center Collaboration
Weizmann Institute of Science—Sheba Medical Center Collaboration
Life Sciences Research Foundation
Horizon 2020 Framework Programme
Chief Scientist Office
European Research Council
Israel Science Foundation119034, 619/16
Israeli Centers for Research Excellence41/11
Office of the Chief Scientist, Ministry of Economy
Horizon 2020757743

    Keywords

    • Schistosoma
    • Th cells
    • extracellular vesicle
    • miRNA

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