CD4 and infection: In this study, we found that PD-1 was activated in splenic CD4+ T-cells upon C. hepatica infection and was highly boosted at the late stage of infection (6 weeks post-infection), indicating the C. hepatica infection induces immune regulation in the host, especially after the adult worms have developed and eggs have been laid in the infected liver, which is coincident with an increase in M2 macrophages in the infected liver at the same time (Figure 1 and Figure 2).