Dynamic changes of T helper responses and hepatic granuloma development during Schistosoma japonicum infection / 中华传染病杂志

ABSTRACT

ObjectiveTo investigate the dynamic changes of T helper (Th) responses and hepatic granuloma development during Schistosoma japonicum infection and to evaluate the possible correlation between the Th1/Th2 cytokines and pathological liver damage. MethodsSera from both Schistosoma japonicum infected C57BL/6 mice and uninfected controls were measured for interferongamma (IFN-γ), interleukin (IL)-4 and IL-13 at week 4, 6, 8 and 12 post-infection. At the same time, the splenic Th1/Th2 ratio was examined. The development of liver granulomas in infected mice was also observed and the correlation between the cytokines and granulomas were assessed. Wilcoxon test and Spearman rank correlation test were performed for data analysis. ResultsSerum IFN-γ level in infected mice was (2. 835±0. 049) lgpg/mL at week 4 post infection, which was significantly higher than that in controls [(1. 787 ± 0. 174) lgpg/mL, Z= - 2. 646, P = 0. 008]. Thereafter, the level declined after week 6, but remained higher than controls at the end of 12-week experiment (Z= -2.457, P=0. 014). IL-4 and IL-13 levels did not increase until week 6 (Z=-2. 646,P=0. 008;Z=-2. 646,P=0. 008), and peaked at week 8. After soluble egg antigen (SEA) stimulation, splenic Th1/Th2 ratio in infected mice was 0.5 (95％ CI 0. 2-1.2) at week 8 and 0.3 (95％ CI 0. 3-0.6)at week 12 post infection, both of which were significantly lower than those in uninfected controls (week 8 Z=2. 173, P=0.030; week 12Z=2.551, P=0.011). Compared with unstimulated splenic cells, splenic Th1/Th2 ratio after SEA stimulation significantly decreased at week 8 (Z=2. 236, P=0. 025) and week 12 (Z=3. 130, P=0.002). Granulomas were first observed in livers at week 6 and the size kept on increasing. A negative correlation between serum IL-13 and the diameter of liver granulomas was discovered at week 12 post infection (r=0. 636, P= 0. 048). Conclusions Th1 response is dominant during the early stage of Schistosoma japonicum infection.However,followed by oviposition, Thl response declines and meanwhile a strong Th2 response gradually develops. Therefore, Th2 response probably plays a role in the development of hepatic granulomas.