Gene Transcription Profile in Mice Vaccinated with Ultraviolet-attenuated Cercariae of Schistosoma japonicum Reveals Molecules Contributing to Elevated IFN-γ Levels  

作　　者：XiangZHU Zhao-SongZHANG Min-JunJI Hai-WeiWU YongWANG Xiao-PingCAI LeiZHANG Shu-YingHU Lin-LinFU FengLIU ChuanSU Guan-LingWU 

机构地区：[1]DepartmentofPathogenicBiology,NanjingMedicalUniversity,Nanjing210029,China

出　　处：《Acta Biochimica et Biophysica Sinica》2005年第4期254-264,共11页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the Qinglan Award from the Jiangsu Provincial Education Committee (2001);a grant from the National Natural Science Foundation of China (No.30271166)

摘　　要：Vaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models.Our preliminary study on the transcrip- tion levels of IFN-γ and IL-4 in splenic CD4^+ T cells revealed that attenuated cercariae elicited predomi- nantly a Th1 response in mice at the early stage,whereas normal cercariae stimulated primarily Th2- dependent responses.Further analysis on the gene profile of the skin-draining lymph nodes demonstrated that the levels of IFN-γ were significantly higher in vaccinated mice than those in infected mice at day 4,7 and 14 post-vaccination or post-infection.However,for IL-12 and IL-4,the potent inducers of Th1 and Th2 responses,respectively,as well as IL-10,there were no differences over the course of the experiment between the infected and vaccinated mice.To explore the underlying factors that may potentially contribute to elevated IFN-γ in vaccinated mice,the mRNA profiles of the skin-draining lymph nodes at day 4 post- exposure were compared using oligonucleotide microarrays.Within the 847 probe sets with increased signal values,we focused on chemokines,cytokines and relevant receptors,which were validated by semi-quantitative RT-PCR,A comprehensive understanding of the immune mechanisms of attenuated cercariae-induced protection may contribute to developing efficient vaccination strategies against S.japonicum,especially during the early stare of infection.Vaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models.Our preliminary study on the transcrip- tion levels of IFN-γ and IL-4 in splenic CD4^+ T cells revealed that attenuated cercariae elicited predomi- nantly a Th1 response in mice at the early stage,whereas normal cercariae stimulated primarily Th2- dependent responses.Further analysis on the gene profile of the skin-draining lymph nodes demonstrated that the levels of IFN-γ were significantly higher in vaccinated mice than those in infected mice at day 4,7 and 14 post-vaccination or post-infection.However,for IL-12 and IL-4,the potent inducers of Th1 and Th2 responses,respectively,as well as IL-10,there were no differences over the course of the experiment between the infected and vaccinated mice.To explore the underlying factors that may potentially contribute to elevated IFN-γ in vaccinated mice,the mRNA profiles of the skin-draining lymph nodes at day 4 post- exposure were compared using oligonucleotide microarrays.Within the 847 probe sets with increased signal values,we focused on chemokines,cytokines and relevant receptors,which were validated by semi-quantitative RT-PCR,A comprehensive understanding of the immune mechanisms of attenuated cercariae-induced protection may contribute to developing efficient vaccination strategies against S.japonicum,especially during the early stare of infection.

关 键 词：Schistosoma japonicum attenuated cercariae oligonucleotide microarray IFN-Γ CHEMOKINES 

分 类 号：R532.21[医药卫生—内科学] R392[医药卫生—临床医学]