Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation
Autor: | Tal Meningher, Eli Schwartz, Dror Avni, Yiftah Barsheshet, Elya Dekel, Orly Avni, Yechezkel Sidi, Boris Brant, Yifat Ofir-Birin, Neta Regev-Rudzki, Daniel Gold |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Biochemistry
03 medical and health sciences Extracellular Vesicles Mice 0302 clinical medicine Immune system Th2 Cells Genetics medicine Mesenteric lymph nodes T-helper cell differentiation Animals Secretion Molecular Biology Transcription factor 030304 developmental biology Schistosoma 0303 health sciences biology Cell Differentiation Extracellular vesicle Articles Schistosoma mansoni biology.organism_classification 3. Good health Cell biology MicroRNAs medicine.anatomical_structure Female 030217 neurology & neurosurgery |
Zdroj: | EMBO Rep EMBO reports |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |