Abstract
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.
Highlights
IntroductionSchistosomiasis is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma
Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma
S. japonicum stimulates immune responses during all stages of its life cycle, which are activated by Th1, Th2, and Th17 cells [19]
Summary
Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. According to the WHO Report 2017, schistosomiasis transmission was reported by 78 countries, and at least 220.8 million people required preventive treatment in 2017. People become infected when the larval form of the parasite penetrates the skin (during contacting with infested water) after being released from. The larvae develop into adult schistosomes inside the body. Adult worms live in the blood vessels, where the females release eggs. Some of the eggs are passed out of the body in the feces or urine to continue the parasite lifecycle. Other eggs are trapped in body tissues, causing immune reactions and progressive damage to organs [2]
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