Abstract
Schistosome infection persists for decades. Parasites are in close contact with host peripheral blood immune cells, yet little is known about the regulatory interactions between parasites and these immune cells. Here, we report that extracellular vesicles (EVs) released from Schistosoma japonicum are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells. Uptake of S. japonicum EV miR-125b and bantam miRNAs into host cells increased macrophage proliferation and TNF-α production by regulating the corresponding targets including Pros1, Fam212b, and Clmp. Mice infected with S. japonicum exhibit an increased population of monocytes and elevated levels of TNF-α. Reduction of host monocytes and TNF-α level in S. japonicum infected mice led to a significant reduction in worm and egg burden and pathology. Overall, we demonstrate that S. japonicum EV miRNAs can regulate host macrophages illustrating parasite modulation of the host immune response to facilitate parasite survival. Our findings provide valuable insights into the schistosome-host interaction which may help to develop novel intervention strategies against schistosomiasis.
Highlights
Schistosomes are parasitic flatworms belonging to the genus Schistosoma and are the causative agents of schistosomiasis, a neglected tropical disease [1]
Extracellular vesicles (EVs) and their miRNA cargo have been shown to be mediators of intercellular communication involved in the regulation of many biological processes
We demonstrated that EVs released from Schistosoma japonicum (SjEVs) are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells
Summary
Schistosomes are parasitic flatworms belonging to the genus Schistosoma and are the causative agents of schistosomiasis, a neglected tropical disease [1]. Schistosome infection persists for decades suggesting a complex pathogen-host interaction that likely modulates the host immune response. Schistosomes utilize host factors for parasite development. Host hormones (insulin) [2], growth factors (TGF-β) [3,4,5,6] and inflammatory factors [7] have been shown to influence schistosome gene expression, development [8] and metabolism. Several studies have evaluated the effect of excreted/secreted products from schistosomes on the host immune response [11,12,13,14,15], the mechanisms that schistosomes use to modulate the functions of host peripheral immune cells remain to be poorly characterized
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