Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice.

Affiliation

Zhang Y(1), Xiong DH(2), Li Y(3), Xu G(4), Zhang B(5), Liu Y(6), Zhang S(1), Huang Q(1), Chen S(1), Zeng F(4), Guo J(7), Li B(3), Qin Z(7), Zhang Z(1).
Author information:
(1)Department of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, China.
(2)Molecular Biology Research Center, School of Life Science, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
(3)Department of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
(4)Key Laboratory of Control Technique for Schistosoma and Pathogen Infection for Dongting Lake Region, Yiyang Medical College, Yiyang 413002, China.
(5)Department of Epidemic Prevention, Armed Police Hospital of Hunan Province, Changsha, 410008 Hunan, China.
(6)Sichuan Center for Disease Control and Prevention, Chengdu, 610041 Sichuan, China.
(7)Key Laboratory of Parasite and Vector Biology, Ministry of Health; National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai 200025, China.

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.