http://www.abbs.info E-mail: [email protected]

ISSN 1672-9145 Acta Biochim Biophys Sin 2005, 37(4): 254–264 CN 31-1940/Q

---

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

Xiang ZHU, Zhao-Song ZHANG*, Min-Jun JI, Hai-Wei WU*, Yong WANG, Xiao-Ping CAI, Lei ZHANG, Shu-Ying HU, Lin-Lin FU, Feng LIU, Chuan SU, and Guan-Ling WU

Department of Pathogenic Biology, Nanjing Medical University, Nanjing 210029, China

Abstract Vaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models. Our preliminary study on the transcription levels of IFN-g and IL-4 in splenic CD4+ T cells revealed that attenuated cercariae elicited predominantly 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-g 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-g 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 stage of infection.

Key words Schistosoma japonicum; attenuated cercariae; oligonucleotide microarray; IFN-g; chemokines

-----------------

Received: December 15, 2004 Accepted: March 2, 2005

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

*Corresponding authors:

Hai-Wei Wu: Tel, 86-25-86862793; Fax, 86-25-86508960; E-mail, [email protected]

Zhao-Song Zhang: Tel, 86-25-86862774; Fax, 86-25-86508960; E-mail, [email protected]