Parasitology

Biography

Biography: Xi Sun

Abstract

Schistosomes are parasitic worms flourishes in the human host despite the development of a pronounced immune response. Understanding how the immune system deals with such pathogens still daunting challenge. Initiative regulation of host immune response by releasing some schistosome-derived molecules is an important mechanism of immune evasion of Schistsoma japonicum. Previously, our groups have identified a 16-kD secretory protein, Sj16, from Schistosoma japonicum. Sj16 is produced and secreted by all stages of the parasite and confirmed as an important protein in the alleviating of inflammation damage when the cercariae penetrated into the skin and was closely involved in to the immune escape of the Schistosomasis. Using recombinant Sj16(rSj16) protein expressed from E.coil, we demonstrated that this recombinant protein has a potent strong immuno-modulation effect and significantly alleviate rat adjuvant-induced arthritis(AA). Recently, our study have observed that immature DC plused with rSj16 can induce significantly IL-10 production and T-helper 2(Th2)-type responses which not show an increase in expression of co-stimulatory molecules or cytokines while their LPS-induced activation, including expression of MHC-II and co-stimulatory molecules as well as IL-12 production is also suppressed. However, since there are no known homologs of Sj16 in metazoans outside the Schistosoma genus, the relationship between Sj16’s function and IL-10 production are unclear. Hence, in the present study, using antibody neutralization experiment and IL-10-deficent(IL-10 Knockout) mice, we further confirmed that the inhibitory effect of rSj16 on LPS-induced BMDCs is due to its induction of IL-10 production. To understand how rSj16 induce the production of IL-10, we analyzed the sequence and revealed two potential nuclear localization signal(NLS) of Sj16. Further studies showed that N-terminal NLS(NLS1) is both necessary and sufficient for translocation of rSj16 to the BMDC’s nucleus and important for subsequent induction of IL-10 production and inhibition of BMDCs maturation by rSj16. Taken together, our results suggest that rSj16 enter into the nuclear of host cells using the NLS1 and promote the production of IL-10 which mediates the inhibitory effect of rSj16 on LPS-induced BMDCS.