Characterization of Schistosoma japonicum CP1412 protein as a novel member of the ribonuclease T2 molecule family with immune regulatory function. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Ke, Xue-Dan; Shen, Shuang; Song, Li-Jun; Yu, Chuan-Xin; Kikuchi, Mihoko; Hirayama, Kenji; Gao, Hong; Wang, Jie; Yin, Xuren; Yao, Yuan; Liu, Qian; Zhou, Wei
• Is Part Of: Parasites & vectors. Volume 10:Issue 1(2017)
• Page Start: 1
• Page End: 19
• Publication Date: 2017-12
• Subjects: Schistosoma japonicum -- Sj CP1412 -- RNase activity -- Th2 polarizaton -- CD4 + CD25 + Foxp3 + T cell; Parasitism -- Periodicals; Parasites -- Periodicals; Vector-pathogen relationships -- Periodicals; Animals as carriers of disease -- Periodicals; Insects as carriers of disease -- Periodicals; 616.96
• DOI: 10.1186/s13071-016-1962-y
• Languages: English
• ISSNs: 1756-3305

Abstract

Abstract Background Schistosome infection typically induces a polarized Th2 type host immune response. As egg antigen molecules play key roles in this immunoregulatory process, clarifying their functions in schistosomiasis would facilitate the development of vaccine and immunotherapeutic methods.Schistosoma japonicum (Sj ) CP1412 (GenBank: AY57074.1) has been identified as a new member of the RNase T2 family with immune regulatory functions. Methods The expression plasmidSj CP1412-pET28a was constructed and transformed into bacteria for production of recombinantSj CP1412 protein (rSj CP1412)via IPTG induction. The RNase activity ofSj CP1412 was predicted by bioinformatic analysis and confirmed by digesting the yeast tRNA with rSj CP1412.C57BL/6j mice were immunized with rSj CP1412, and its immune regulatory effects in vivo and in vitro were investigated. Meanwhile, the relationship between the RNase activity ofSj CP1412 and its immune regulation was observed. Results Sj CP1412 was confirmed as a novel RNase T2 family protein with RNase activity. Immunoblotting and RT-PCR analyses demonstratedSj CP1412 as a protein exclusively secreted/excreted from eggs, but not cercariae and adult worms. Stimulating RAW264.7 macrophages with rSj CP1412 raised the expression of CD206, Arg-1 and IL-10, which are related to M2 type macrophage differentiation. Stimulating dendritic cells (DCs) with rSj CP1412 failed to induce their maturation, and the recombinant protein also inhibited LPS-stimulated DC maturation. Depletion ofSj CP1412 from soluble egg antigen (SEA) impaired the ability of SEA to induce M2 type polarization of RAW264.7 macrophages. Immunizing mice with rSj CP1412 induced high antibody titers, increased serum IL-4 and TGF-β levels and splenic CD4 + CD25 + Foxp3 + T cells, downregulated serum IFN-γ levels and alleviated the egg granuloma pathology of schistosome infection. In vitro stimulation by rSj CP1412 significantly increased CD4 + CD25 + Foxp3 + T cell numbers in splenocytes of healthy mice. The rSj CP1412 protein with RNase activity inactivated by DEPC failed to induce M2 surface marker CD206 expression in RAW264.7 macrophages. Conclusions TheSj CP1412 protein expressed specifically inS. japonicum eggs is a novel member of the RNase T2 family. Similar to Omega-1 ofSchistosoma mansoni, theSj CP1412 protein drives polarization of the host Th2 immune response, which is dependent on its RNase activity. These data provide new evidence towards understanding the immune regulatory role of RNase T2 family proteins during schistosome infection.