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

EMBO Reports - Tập 21 Số 1 - 2020
Tal Meningher1,2, Yiftah Barsheshet3, Yifat Ofir‐Birin4, Daniel Gold5, Boris Brant3, Elya Dekel4, Yechezkel Sidi6,1, Eli Schwartz6,2,7, Neta Regev‐Rudzki4, Orly Avni3, Dror Avni1,2
1Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel
2Molecular Laboratory for the Study of Tropical Diseases Sheba Medical Center Tel Hashomer Israel
3Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
4Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
5Department of Clinical Microbiology and Immunology Faculty of Medicine Sackler School of Medicine Tel Aviv University Tel Aviv Israel
6Faculty of Medicine Sackler School of Medicine Tel Aviv University Tel Aviv Israel
7The Center for Geographic Medicine Sheba Medical Center Tel Hashomer Israel

Tóm tắt

AbstractDuring 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.

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