Cysteine protease inhibitor of Schistosoma japonicum - A parasite-derived negative immunoregulatory factor.

Abstract

Studies have shown that cysteine protease inhibitors from some parasites have immunosuppressive effects on the host. We previously have cloned a novel cysteine protease inhibitor from Schistosoma japonicum and purified its recombinant version (protein named rSj-C). Its possible inhibitory effect on the host immune response has not been described.This study shows that rSj-C inhibits lysosomal cysteine protease of murine dendritic cells (DCs). After DCs were incubated with rSj-C and then with soluble adult worm antigen (AWA) of S. japonicum, the mean fluorescence intensity of MHC class II antigens on the surface of DCs decreased significantly by flow cytometry. These results indirectly proved that rSj-C can suppress exogenous-antigen presentation by DCs. The flow cytometric assay revealed that in comparison with control groups, the proportion of CD4+CD25+Foxp3+ T cells among CD4+CD25+ T cells of Schistosom-infected mice increased significantly 8weeks after the infected mice were injected with rSj-C (p˂0.05). Additionally, the expression levels of cytokines IL-4 and TGF-β produced by T cells increased significantly as compared with these levels in the normal group (p˂0.05). These results clearly show that the cysteine protease inhibitor from S. japonicum is a new parasite-derived immunosuppressive factor.