Schistosomes- exosomal miRNAs: modulators of T helper (CD+) cell differentiation

ABSTRACT: Schistosomiasis (Bilharziasis) is caused by the helminth Schistosoma. The acute stage of the infection extends from the penetration of the parasite through the host skin until it reaches its final location as adult female and male in copula, at the blood vessels around the gut or bladder. The female starts then depositing fertile eggs. The chronic stage of schistosomiasis starts with laying the eggs which promote a strong immunological Th2 response. It is unclear, so far, how this Th2 response gradually declines even though the parasitic worms live for years and continue to produce eggs. Here we demonstrate that schistosomes downregulate the differentiation toward the Th2 lineage by modulating the Th2 transcriptional program. Moreover, we found that adult schistosomes secrete micro-vesicles, possessing exosomal characteristics, and containing miRNAs, which have been found in Th2 cells that exposed indirectly to schistosomes. Importantly, we demonstrate that, the schistosoma miR-10 molecule targets MAP3K7, which consequently down modulates NF-kB. Since NF-kB is a critical factor necessary for Th2 differentiation and function, our results can at least partially explain, the decrease of the Th2 response over time of infection This exosomal worm-host immune cell interaction, can be further utilized for the development of novel diagnostic and therapeutic approaches to schistosomiasis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Bos Taurus (bovine)

SUBMITTER: Tamar Ziv  

LAB HEAD: Dror Avni

PROVIDER: PXD012525 | Pride | 2019-12-10

REPOSITORIES: Pride