SjCRT, a recombinant Schistosoma japonicum calreticulin, induces maturation of dendritic cells and a Th1-polarized immune response in mice

Lizhen Ma,Dandan Li,Xingang Feng,Xiaochao Zhao,Chunxiu Yuan,Xiangqian Zhang,Yumei Li,Na Ta

doi:10.1186/s13071-017-2516-7

Abstract

BackgroundIt is well known that immunization of radiation-attenuated (RA) schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. However, the molecular mechanism of this strong protective immunity remains unclear.MethodsThe expression profiles of Schistosoma japonicum calreticulin (SjCRT) in RA and normal schistosoma-derived cells were investigated by flow cytometry. The effect of recombinant SjCRT (rSjCRT) on mouse dendritic cells (DCs) was determined by FACS, ELISA and RT-PCR analysis. We also analyzed the effects of SjCRT on the activation of spleen cells from mice immunized with rSjCRT by detecting lymphocyte proliferation and the cytokine profiles of splenocytes.ResultsWe found that the expression level of SjCRT in the cells from RA larvae was significantly higher than that in cells from normal schistosomula at early stages of development (day 4). The results of effect of rSjCRT on mouse DCs showed that rSjCRT could induce phenotypic and functional maturation of DCs, and SjCRT bound to the surface of DCs through the CD91 receptor and could be engulfed by DCs. The results of activation of splenocytes from mice immunized with rSjCRT also demonstrate that rSjCRT can effectively stimulate the proliferative response of splenic lymphocytes, elicit splenocytes from immunized mice to secrete high levels of IFN-γ, TNF-α and IL-4, and activate CD4+ T cells to produce high levels of IFN-γ.ConclusionSjCRT is one of the immunostimulatory molecules released from RA schistosomula cells, might play a crucial role in conferring a Th1-polarized immune response induced by RA cercariae/schistosomula in mice, and is a candidate molecule responsible for the high levels of protective immunity induced by RA schistosomula.

Highlights

It is well known that immunization of radiation-attenuated (RA) schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals
We show that the expression level of Schistosoma japonicum calreticulin (SjCRT) in early stage RA schistosomula was significantly higher than that in cells from normal parasites, and SjCRT could induce the maturation of Dendritic cells (DC) and facilitate a Th1-skewed immune response in mice
The results of immunoblotting demonstrated that the recombinant protein can be recognized by the serum of mice infected with S. japonicum (Fig. 1, Lane 2), the antiserum from mice immunized with recombinant SjCRT (rSjCRT) reacted with a crude adult worm antigen of 55 kDa (Fig. 1, Lane 4), suggesting that rSjCRT has good antigenicity and that sera against rSjCRT can be used to determine the expression profile of SjCRT in the cells from normal and RA schistosomula

Summary

Introduction

It is well known that immunization of radiation-attenuated (RA) schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. The molecular mechanism of this strong protective immunity remains unclear. In order to sustainably control schistosomiasis, there is an urgent need to develop prophylactic vaccines with high efficacy and safety. Previous studies have indicated that vaccination with radiation-attenuated (RA) larvae is highly effective in many experimental hosts. Researchers propose that a molecular vaccine against schistosomiasis might be developed according to the effective mechanisms of protective immunity induced by an RA vaccine [2, 3]. Further analysis of the mechanisms of protective immunity showed that irradiated lung-stage schistosomula

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Discussion

Conclusion