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

摘要

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 3rd 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.