Ultraviolet- attenuated cercariae of Schistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice

Objective: To better understand the reason that Schistosoma japonicum (S. japonicum) ultraviolet (UV)-radiated cercariae could not induce high level of protection in C57BL/6 mice.

Methods: Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes (sdLNs) at 1 w after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC-infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure.

Results: The gene expressions of Th1 cytokines, including interferon-γ (IFN-γ), interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3(rd) w after vaccination with UV-AC.

Conclusion: UV-AC of S. japonicum could not effectively induce a Th1 response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated.