Recombinant Sj16 from Schistosoma japonicum contains a functional N-terminal nuclear localization signal necessary for nuclear translocation in dendritic cells and interleukin-10 production

Abstract

Sj16 is a Schistosoma japonicum-derived protein (16 kDa in molecular weight) that has been identified as an immune modulation molecule, but the mechanisms of modulation of immune responses are not known. In this report, we aimed to investigate the host immune regulation mechanism by recombinant Sj16 (rSj16) and thus illuminate the molecular mechanism of immune evasion by S. japonicum. The effect of rSj16 and rSj16 mutants on the biology of dendritic cells (DCs) was assessed by examining DC maturation, cytokine production, and expression of surface markers by flow cytometry and enzyme-linked immunosorbent assay. We found that rSj16 significantly stimulated interleukin (IL)-10 production and inhibited LPS-induced bone marrow-derived dendrite cell (BMDC) maturation in a dose-dependent manner. By using antibody neutralization experiments and IL-10-deficient (knockout) mice, we confirmed that the inhibitory effect of rSj16 on LPS-induced BMDCs is due to its induction of IL-10 production. To understand how rSj16 induces the production of IL-10, we analyzed the protein sequence and revealed two potential nuclear localization signals (NLS) in Sj16. The N-terminal NLS (NLS1) is both necessary and sufficient for translocation of rSj16 to the nucleus of BMDCs and is important for subsequent induction of IL-10 production and the inhibition of BMDC maturation by rSj16. The results of our study concluded that the ability of rSj16 to inhibit DC functions is IL-10 dependent which is operated by IL-10R signal pathway. This study also confirmed that NLS is an important domain associated with increased production of IL-10. Our findings will extend the current understanding on host-schistosome relationship and provide insight about bottleneck of parasitic control.

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